The dangers of over-analyzing too much data in prostate study

In the last week there has been a constant buzz about an online pre-publication of a new research article that suggests that high concentrations of omega-3 fatty acids promote aggressive prostate cancer (1). Well, that really isn’t the case, in spite of the press reports. That’s why you have to carefully read the article before jumping to conclusions.

Prostate cancer, like all cancers, is driven by cellular inflammation. The level of cellular inflammation is defined by the AA/EPA ratio of isolated serum phospholipids. When you analyze the data correctly in that article, you find that there was no difference in the AA/EPA ratio between the low-aggressive, high- aggressive, or control group. In fact, all the groups had the same elevated AA/EPA ratio of 18.8. Since I like to have individuals try to maintain an AA/EPA ratio of less than 3, all of these groups could be considered to be inflamed.

Not surprisingly, when you look at either EPA or AA levels separately in each group, they are identical. It’s only when you look at the DHA levels, do you see a small difference statistically, but it’s meaningless clinically. There was a 2.5 percent increase in the DHA levels in the high-aggressive group compared to the control group. In the paper, authors state their error in measuring DHA is ± 2.4 percent. Call me crazy, but I don’t see the big difference between the reported results and their error measurements. To further cloud the results, the authors also find that the levels of trans-fatty acids are lower in the aggressive prostate cancer patients than the controls. So I guess if you wanted to take their data at face value, DHA makes prostate cancer more aggressive and trans-fatty acids found in junk foods make prostate cancer less aggressive.

I believe this is simply a case of over-interpretation of massive amounts of collected data. If you get enough data points, you can always make some type of correlation, but that’s all it is. At some point you also have to allow common sense to enter the final analysis.

Nonetheless, let’s say their data might be correct. How could excess DHA increase the aggressiveness of any cancer? Well, it might decrease the levels of dihomo gamma linolenic acid (DGLA) as I have explained in many of my books (2-5). DGLA is the building block for a powerful group of anti-inflammatory eicosanoids, and its formation is inhibited by DHA. Depressing DGLA levels would reduce the body’s ability to hold back the inflammation that drives the tumor. Unfortunately, with all the data they accumulated, they forgot to publish the changes in the DGLA levels in the various groups. Oops.

So even if there were not any changes in the AA/EPA ratio between groups, a depression of DGLA levels in the aggressive prostate cancer group would easily explain the clinical observation. Unfortunately, that interpretation requires an extensive background in understanding eicosanoid biochemistry, which is not easily found in academic clinical-research centers.

This is not the first time that the potential benefits of DHA are in question. In the largest cardiovascular intervention study ever done, it was demonstrated that adding high levels of EPA to the diet of Japanese patients with high cholesterol levels (who already with a very low AA/EPA ratio of 1.6), dramatically decreased their likelihood of future cardiovascular events (6). This reduction was only correlated with increases in EPA levels as well as with a decrease in the AA/EPA ratio from an already low 1.6 to an even lower 0.8 (7). The levels of DHA in these patients had no significance for predicting future cardiovascular events.

Likewise other studies using DHA alone to treatment post-partum depression, improve neurological functioning of children or treating Alzheimer’s have also been found to be negative (8,9).

It’s not that DHA is bad, it just doesn’t do much to reduce cellular inflammation. DHA does a lot of other useful things, but reducing cellular inflammation in not one of them.

References

  1. Brasky TM, Till C, White E, Neuhouser ML, Song X, Goodman P, Thompson IM, King EB, Albanes D, and Kristal AR. “Serum phospholipid fatty acids and prostate cancer risk.” Amer J Epidem 173: doi 10:1093/aje/kwr9027 (2011)
  2. Sears, B. “The Zone.” Regan Books. New York, NY (1995)
  3. Sears, B. “The OmegaRx Zone.” Regan Books. New York, NY (2002)
  4. Sears, B. “The Anti-inflammation Zone.” Regan Books. New York, NY (2005)
  5. Sears, B. “Toxic Fat.” Thomas Nelson. Nashville, TN (2008)
  6. Matsuzaki M, Yokoyama M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, and Matsuzawa Y. “Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease.” Circ J 73:1283-1290 (2009)
  7. Itakura H, Yokoyama M, Matsuzaki M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, and Matsuzawa Y. “Relationships between Plasma Fatty Acid Composition and Coronary Artery Disease.” J Atheroscler Thromb 18:99-107 (2011)
  8. Makrides M, Gibson RA, McPhee AJ, Yelland L, Quinlivan J, and Ryan P. “Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial.” JAMA 304; 1675-1683 (2010)
  9. Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR, Weiner M, Shinto L, and Aisen PS. “Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial.” JAMA 304: 1903-1911 (2010)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.

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About Dr. Barry Sears

Dr. Barry Sears is a leading authority on the impact of the diet on hormonal response, genetic expression, and inflammation. A former research scientist at the Boston University School of Medicine and the Massachusetts Institute of Technology, Dr. Sears has dedicated his research efforts over the past 30 years to the study of lipids. He has published more than 30 scientific articles and holds 13 U.S. patents in the areas of intravenous drug delivery systems and hormonal regulation for the treatment of cardiovascular disease. He has also written 13 books, including the New York Times #1 best-seller "The Zone". These books have sold more than 5 million copies in the U.S. and have been translated into 22 different languages.

27 thoughts on “The dangers of over-analyzing too much data in prostate study

  1. Dr Sears, I like your info. BUT, your bagel chips have a lOT of salt in them (not necessary)

    I don’t like sucralose. do you?

    Also, will you have any gluten-free products?

  2. As a recent study in JAMA has pointed out, our desire to reduce salt intake may not be justified. The salt in the bagel chips comes from the herbs that are being added. The bagel chips themselves come from Zone bagels that have limited amounts of salt.

    The reason for the artificial sweetener is to reduce the taste of vinegar that increases the shelf life of the bread products at room temperature. Our next generation of bread products will have no artificial sweeteners as we perfecting out baking technology.

    My wife is severely gluten intolerant so I have a constant domestic driving force to develop gluten free products. Unfortunately gluten is the only ingredient that allows us to give the flour elastic properties necessary to make bread.

  3. Dr. Sears: Read a response last night to “The Dangers of Over-analyzing too much Data in Prostate Study” by someone who developed prostate cancer. Now I can’t seem to access that response or your response to it, if you did respond…

  4. Joe,
    It was I who posted the response that was deleted.

    How dare you, Dr. Sears.
    I can’t wait until next year’s cruise. See you then, buddy!

    • I checked with the site administrators. Your post was not deleted, nor can they find a record of it.

      I truly resent the implication that any post would be deleted as I personally make every effort to clarify everyone’s questions and comments.

  5. Thanks, Jockobono,
    I really wanted to read his response. I don’t get why he deleted it. Being a man like you, prostate health is a concern for me, although my yearly physical last week revealed a healthy one, knock on wood. Sorry that your dealing with it. Are you currently taking fish oil or has the new literature given you second thoughts?
    Regards,
    Joe

  6. Prostate cancers feed only on testosterone. The lower the testosterone, the less risk of cancer. Once you have a cancerous tumor, the treatment is to, first, block the testosterone to starve the tumor and then get rid of the tumor. I had radiation treatments, 44, and my PSA dropped from 10 to 0. Since December, my PSA has remaind at 0. I go for a follow-up at the radiation center today. I also take Dr. Sears Omega 3, I take 6 a day and I feel marvelous, at 76 years of age.

  7. The recommended dose normally is 4 a day. For cancer patients it is 12 a day.
    I contacted a Sears representative and asked how many I should take due to the fact that I both had cancer but no inflammation and the 12 a day would not apply to me. The representative
    suggested 8 a day (more than a normal dose but less than recommended )
    My problem with Dr Sears is that he doesn’t make allowences. Everything about Dr Sears is absolute. And he is wrong. There are no absolutes. I am living proof.

    • I am afraid that you don’t have a clear understanding of my work and my suggested dietary guidelines. You try to bring your level of AA/EPA in the blood to between 1.5 and 3 to manage cellular inflammation. The amount of omega-3 fatty acids to achieve depends on your genetics, your diet, and the extent of your condition. Everyone is different because as you say, “there are no absolutes”.

  8. Moreover, since I didn’t answer your actual question of taking 6 a day, after my cancer treatments proved a success, I cut back to the normal dose of 4 a day but I got to thinking on my own that since I continue to get testosterone blocking injections and will get these for another year to be on the safe side as deemed necessary by my radiation team, I decided to increase my dose to 6 and it proved to be an amazing experience. My weight is dropping, my energy has increased, my hair is growing at a much gfaster rate, my nails are growing like crazy, my stools float, my need for sleep has decreased tremendously, my appetite is greatly reduced, and I could go on and on.
    Dr.Sears lumps everybody into one catagory. This is assinine. Everybody is an individual but Sears does not treat them this way. Sears make no allowences.

  9. I found some additional information that wasn’t made clear in the study (don’t remember with 100% certainty since I’m a definite “information collector”, but think it might have been an interview with the lead researcher conducted by the Life Extension organization). These were not people who were taking a high quality fish oil supplement. They were getting their omega-3′s from fish alone–I believe twice a week. So–what was the rest of the diet like? What would the results have been if they properly decreased their inflammation levels? Again, if you’re in doubt, and you want verification of what Dr. Sears is saying, just got to the NIH website, and go to EFA education.

  10. Karen,
    I AM 100% SURE that Dr.Sears said that prostate cancer is driven by inflammation and I would like Dr. Sears to explain why mine was NOT! As soon as I learned I had prostate cancer, I had my inflammation tested TO SEE HOW MUCH INFLAMMATION I HAD and it tested perfect, in fact TOO PERFECT. Inflammation is caused by too much Omega6 and not enough Omega3 to balance it out. I was not eating enough Omega6 and a Sears representative suggested I eat more egg yolks to get more Omega6 to bring my AA/EPA in balance. Karen, I am not in any doubt that Dr.Sears is wrong on this issue.Why was my comment deleted?
    I am going on next years cruise and show everybody on the cruise the print outs of my biospy of 7 tissue samples showing cancer and the print outs sent to my by the lab showing no inflammation and there and then Dr. Sears will have to reply.

    • Cancer takes decades to develop. I frankly doubt that you have following the Zone diet and taking adequate levels of omega-3 fatty acids for decades. You should be quite happy to have your current PSA at 0 since after surgery the PSA level becomes highly predicative of cancer metatasis. If you want to keep you keep you PSA low, I would suggest you continue to follow an anti-inflammatory diet.

  11. Thanks for your comments, Jockobono. I wondered if you tried other fish oil supplements? Dr. Sears seems to claim that his are the best. I’ve been trying the Life Extension f.o. that includes sesame and olive oil, but I can’t really tell much of a difference. In your opinion, are the Sears f.o. the best? He seems to say that you also have to have his polyphenols in order to keep the f.o. from going rancid. Your thoughts?

  12. There has been a lot of information, lately – about how astaxanthin with Fish oil is much, much better than Fish Oil alone. What does Dr. Sears say about this?
    Problem is most Fish Oil with astaxanthin is a low-grade at 1000mg with only 200+/100+ EPA/DHA, and not the higher grade 400/200 ratio of EPA/DHA.
    So, is Dr. Sears considering adding Astaxanthin to his Fish Oil?
    OR is taking a separate Astaxanthin just as effective?

    • I always recommend consuming adequate levels of polyphenols to protect omega-3 fatty acids from oxidation at the level of about 2,500 ORAC units for every 2.5 grams of EPA and DHA you take on a daily basis. Polyphenols are more powerful antioxidants than astaxanthin since polyphenols are amipathic molecules that sit at the lipid interface of membranes. On the other hand, astaxanthin is a carotene that is lipid soluble and not amipathic. Since much of oxidation takes place at the membrane interface the positioning of the polyphenol at the surface of the membrane makes it a more effective in protecting the omega-3 fatty acids in the membrane.

      Adding any anti-oxidant to a fish oil product is not recommended since at higher levels, the excess anti-oxidant can become a pro-oxidant that accelerates oxidation of the omega-3 fatty acids while they are still in the capsule. It is best to keep the omega-3 fatty acids separate from any supplemented anti-oxidants, but take them at the same time.

  13. Dr. Sears,
    I am always curious about the methodology of health studies when I see headlines. It makes me wonder about the review process at the design stage. How much more useful could these large scale studies be if they tracked only a few more points of data? And then I often think that the conclusions are incorrect extrapolations of the data that is collected. I hope that more peer reviewed journals will allow their studies to be read online without requiring hefty document fees someday.

    On gluten free baking, I find that tapioca starch, guar gum, and xantham gum can add all the chewiness and stickiness that is lost by using grains without glutens in them.

    • Unfortunately clinical trials are expensive so the number of subjects are limited. In addition, the starting hypothesis is rarely achieved, so subgroup analysis is often done to extract any time of data that can be published to justify the cost of the trial. This is why you have to read the entire article. I am fortunate that I have access to every research publication, a luxury not available to the general public or most science writers who only have access to limited abstracts.

  14. Joe,
    I primarily take Sears Eico/Rx because something tells me they are the best, especially that they contain GLA but I don’t like the price yet I do get a huge discount buying recurringly.
    I take his Polyphenol/Plus because of them being anti-oxidents. I take Eden Selected Toasted Sesame Oil, 1 tsp/day. I think it’s silly to take a supplement containing olive oil. Olive oil is abundant otherwise and the amount in a supplement is neglible, as is sesame oil or olive oil in any supplement. I do supplement Sears Omega3 with a lesser costing Dr. Murray’s Pharmaceutical Grade RxOmega-3, basically identical to Sears at nearly half the price.
    I can’t help trusting Sears products. Sears’ products have been around a long time. I’m skeptical of these newly promoted wonder products that come and go.

  15. Thanks, Jockobono and Dr. Sears. I’ll stop the LEF fish oil with the added sesame and olive oil. I have to confess that I don’t know a whole lot about these things. My PhD is in theatre, and I’m a professor of acting. However, I’m very concerned about my health and well being. I’m 54 years old and my mom died of cancer at 44 and my brother died of cancer at 37. I was a smoker but quit and started the Zone diet about 7 years ago when my GP recommended it. I studied the books and the eye method of dividing the plate into thirds, 1/3 protein, 2/3 carbs has worked well for me. What attracts me to Dr. Sears’s approach is it’s simplicity. I started getting into fish oil after reading the literature. My yearly physicals have all produced good results. I’m about 136 pounds, 5’6″ and I’ve always exercised since I was a kid, through my years in the Marines, etc. I am assuming that what’s best for me is to take 4 fish oil pills per day along with a polyphenol supplement. Does this sound about right or would either of you suggest anything else? Are these Dr. Murray’s f.o.’s and different from Dr. Sears’s f.o.? Are any polyphenol supplements good or is Dr. Sears’s the one to take? What about all this literature on taking a baby aspirin per day? Lot’s of questions, I know. But life can be short, so let’s make it long.
    -Joe

  16. Who to believe! I made the decision to believe Dr. Sears standards for fish oil. I was registered at Dr. Sears first website “The Zone Files” in the late “90′s. Long story that I won’t get into but a good story none the less. I’ve been creating Zone recipes since then. Purity of consumed fish oil is essential, especially in large quantities. Dr. Murrays, as I said before, is, i’d say, identical to Sears but maybe not as pure, but, again, I’d say safe in normal quantities, like 4 a day. Dr. Sears guarantees his fish oil – Omega 3 – is safe, regardless how many you take. As of today, I wouldn’t take any other brand Omega3 supplement other than these 2.
    I had a bone scan for signs of cancer and density. Results showed osteopenia, naturally, at 76 yrs old and lack of calcium intake and my doctor put me on Oyster shells and D. Soon after I started taking Dr. Sears brand, only $4 a mo. more but Sears brand contained all the forms of calcium, not just one.

  17. Dr Sears is the fact that Omega Rx contains no DGLA a drawback? How can we balance our DGLA levels to avoid the adversities of DHA?

      • Dr. Sears,
        Question 1: When you suggest adding one EicoRx per day does that mean in addition to the 4 capsules per day for the average healthy person or substituting one of the 4 OmegaRx?
        Question 2: For the average person, how much oatmeal per week could replace that one EicoRx you recommend?

  18. Dr. Sears,
    I have seen you say, in the past, that too much GLA is not a good thing and not to eat slow cooking oatmeal every day but to limit it to every other day or so and that, you said, slow cooking oatmeal is the best food souce of GLA. Am I correct? Assuming I am correct, what about those, like me, who are taking large doses of EicoRx? Presently I take 6 capsules of EicoRx per day. You recommend 12 capsules of your Omega3 per day for cancer patients. Does this include, or not, your EicoRx?

    • It totally depends on the genetics of the individual. Some can be lucky with GLA, others not so lucky. I usually recommend adding one capsule of EicoRx each day to the level of OmegaRx capsules you are already taking as an insurance policy. Nonetheless, that still may be too much for an individual. The best way to determine that amount of EicoRx is to follow my eicosanoid status report found in the Resource section of http://www.drsears.com.

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