Drs. Bill Harris and Rhonda Patrick comment on omega-3 prostate cancer study SELECT trial
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In this clip, Drs. Bill Harris and Rhonda Patrick discuss a questionable, potentially spurious association between omega-3 and selenium supplementation and prostate cancer. While omega-3 is more well-known for generally promoting cancer protection, the 2008 SELECT trial seemed to show something alarming: an association between vitamin E, omega-3, and selenium supplementation and prostate cancer. Rather than omega-3 as a culprit, Dr. Patrick spotlights an important confounder that may partly explain the results of this isolated study. Participants in the study took nearly 20x RDA mega-doses of alpha-tocopherol, a form of vitamin E that may have unique and potentially detrimental effects that could account for this association.
Dr. Patrick: So there's a few more things that I would kind of love to get your thoughts on.
Dr. Harris: Sure.
Dr. Patrick: One is a question a lot of people will ask me or email me about...and it is about this 2013 paper that was published by Brasky.
Dr. Harris: Yeah. Brasky. Ted.
Dr. Patrick: Yes. And he looked at blood omega-3 levels. I don't know if it was plasma phospholipid.
Dr. Harris: Plasma phospholipid.
Dr. Patrick: Yeah. Omega-3 and the incidence of prostate cancer in a trial of people, it was called the SELECT trial where people were given high doses of tocopherol and/or selenium. And he found a correlation between the plasma phospholipid omega-3 and prostate cancer.
Dr. Harris: And it was statistically significant. It was...the range of high to low omega-3 was like this, like 4.6% versus 4.2%. Something like that. It's very, very, very narrow, very small, which makes it go well. That doesn't make any sense. Plus, I mean, my biggest... I don't criticize the results so much as the discussion in that paper because they said, therefore, ergo taking fish oil or eating high omega-3 fish is going to cause prostate cancer. They turned, A, an association into a cause and effect. In that study, you weren't allowed to be on an omega-3 supplement. Nobody in that study was on omega-3. These guys already had a bent that they didn't...they wanted to show something bad about them, supplements in general and omega-3 happened to be supplement du jour. And so their discussion and what they said on TV and what they said on other interviews was what went way beyond the data. The data itself have not been confirmed.
They'd been refuted by other studies. Those studies don't get any press, of course, and you're left with this weird thing hanging out from now, eight years ago that still pops up that, you know, hopefully this podcast will not cause somebody to go look at, because if you do look at it, realize that the levels of omega-3 are very tiny. Plus, I mean, we submitted a letter to the editor about that, me and Michael Davidson. And one of the things we pointed out was there's evidence that in some cancer cells, they can actually upregulate FADS activity and you might actually be making some more omega-3 because you got cancer. If, I mean, again, it's a very tiny difference in levels between those who did and those who didn't get cancer. But there are other mechanisms, one, if it was even true, then that you can explain it by.
Dr. Patrick: And once you have expected it to be repeated with yet, there were other studies, as you mentioned, that refuted that showed that actually omega-3s were more protective of even prostate cancer. But I don't know if...you want to know my thoughts too on this with the SELECT trial?
Dr. Harris: Yeah, sure. Am I allowed to ask right now?
Dr. Patrick: I mean, so, you know, the fact, the trial design, the fact that these men were actually...they were given, like, it was 400 IUs of alpha-tocopherol or selenium. I mean, the 400 IUs of alpha-tocopherol, my mentor Bruce Ames and one of his post-docs had shown that when you give a high dose of alpha-tocopherol much like... The RDA of it is like 25...
Dr. Harris: Fifteen milligrams. Yeah.
Dr. Patrick: Something like that. Yeah. That you basically deplete another tocopherol, gamma-tocopherol, which is anti-inflammatory. And so there's this, you know, it's actually not good to take mega doses of the vitamins...
Dr. Harris: The alpha-tocopherol.
Dr. Patrick: The alpha-tocopherol hormone, vitamin E. And so it's like, you're looking at blood samples from a very confounded, you know, cohort.
Dr. Harris: You're assuming a selenium and alpha-tocopherol had no effect on its outcome. Right.
Dr. Patrick: Right. And we have no idea what could have happened, right?
Dr. Harris: I didn't know that. That's interesting.
Dr. Patrick: Yeah. And then plus the lack of confirmation of that study, it's just...I kind of want to like, you know, get this out there. I mean, this study, it was...
Dr. Harris: Right. Do not believe this study. Do not let them.
Dr. Patrick: Yeah. You know, it was a sensational headline as anything that is thought to be good for you but then it's not good for you and not only not good, could be bad for you, you know?
Dr. Harris: Totally. They love this.
Dr. Patrick: Yeah. It makes the headlines.
Dr. Harris: Glad we got that taken care of.
One of the eight forms of vitamin E. Alpha-tocopherol, a potent fat-soluble antioxidant that plays roles in cell signaling and gene regulation, is the form of vitamin E that is preferentially absorbed and stored in humans. Dietary sources of alpha-tocopherol include nuts, seeds, and vegetable oils.
Rate-limiting enzymes in the biosynthesis of monounsaturated fatty acids and polyunsaturated fatty acids (PUFAs). FAD enzymes remove hydrogen from a single carbon bond in order to form a double carbon bond. They play critical roles in the desaturation and elongation cascades that convert PUFAs to long-chain PUFAs.
One of the eight forms of vitamin E. Gamma-tocopherol exerts potent antioxidant and anti-inflammatory properties. It is the most abundant form of vitamin E in the diets of people living in the United States. Dietary sources of gamma-tocopherol include nuts and seeds.
A type of polyunsaturated fat that is essential for human health. Omega-3 fatty acids influence cell membrane integrity and affect the function of membrane-bound cellular receptors. They participate in pathways involved in the biosynthesis of hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They have been shown to help prevent heart disease and stroke, may help control lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions. Omega-3 fatty acids include alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA is found mainly in plant oils such as flaxseed, soybean, and canola oils. DHA and EPA are found in fish and other seafood. The human body can convert some ALA into EPA and then to DHA, but the efficiency of the process varies between individuals.
The daily nutrient goals for essentially all healthy people. RDAs are calculated by determining the Estimated Average Requirements (the average amount of nutrients that half of all healthy people in any given demographic need each day) and adding two standard deviations. This ensures that the RDAs exceed the requirements of approximately 97.5% of the population.
An essential trace mineral. Selenium is incorporated into selenoproteins, a class of highly conserved proteins that exert potent antioxidant activity. Selenoproteins play critical roles in reproduction, thyroid hormone metabolism, DNA synthesis, and protection from oxidative damage and infection. One of the best-known selenoproteins is glutathione peroxidase. Selenium can be obtained from supplements and foods such as Brazil nuts, yellowfin tuna, beans, and some grains.
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