Fish oil is in the news again, thanks to reports about a research study conducted by Dr Theodore M. Brasky and colleagues linking high blood levels of the fish oil constituents EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) to an increased risk of high-grade prostate cancer in American men. This study has been the subject of a great deal of commentary and criticism, in both mainstream and “alternative medicine” media outlets. Understandably, it has many patients quite concerned, and several have asked if they should discontinue their use of fish oil supplements. Let’s take a look at this study, and some of the concerns that have been raised about the study’s methodology, which are prompting several of us to call its conclusion into question:
- It’s important to keep in mind that this was not a randomized study in which men were given fish oil or assigned a high-fish diet. It was an observational study, and while it provides a possible hypothesis for consideration, it does not prove any direct connection between EPA and DHA and prostate cancer.
- One single blood sample taken at one point in time may have little relevance to what happens over the next several days and weeks, let alone the next several years, that might increase or decrease risk of prostate cancer.
- The patients who had prostate cancer were found to have higher levels of risk factors, such as being overweight or having a family history of prostate cancer. We have no way of knowing how these additional risk factors might have contributed to these patients’ diagnoses.
- Brasky and colleagues have no dietary data on these patients, and only a small minority of them were actually taking fish oil, so it’s hard to know how to relate the EPA and DHA contents to what men actually were ingesting. I will go into detail regarding why the lack of dietary data is of considerable relevance later in this blog.
- The plasma phospholipid analysis used to determine levels of EPA and DHA in the blood is quite unstable, and variable from day to day. Meaning, had this analysis been done a mere 24 hours later than it was actually done, it might have provided a very different result.
- The men in the study were found to have rather low levels of omega-3s to begin with, and the difference between the levels in the high-grade prostate cancer group and the others actually turned out to be very small, 0.02%. The low levels may indicate that these men had diets that were suboptimal in omega-3 content to begin with.
- There are also more technical aspects of the study that are concerning. There was no regular schedule of prostate biopsies in the study, so some of those not diagnosed with prostate cancer could actually have had undetected cases.
- The assignment of patients to “high” and “low” grades of prostate cancer is questionable at best. Clinically there are three grades of prostate cancer, low, intermediate and high. Some of the intermediate patients were assigned to high grade, and others were assigned to low grade, based on a rationale that has been called into serious question.
- Finally, the authors did not present a strong mechanism by which fish oil or fish could increase prostate cancer risk.
The subjects in this study were participating in the famous SELECT trial, in which men were given alpha-tocopherol and selenium, which failed to demonstrate any benefits regarding prostate cancer prevention. Brasky and colleagues obtained blood samples taken at the start of the study and compared EPA and DHA levels in study patients who later developed prostate cancer to those men who were also in the study but never got prostate cancer. They tested plasma phospholipid EPA and DHA levels, rather than red blood cells, prostate tissue or other measures that have been used in other studies. Men with high-grade prostate cancer, which has more malignant features than low grade prostate cancer, had levels of EPA and DHA that were a few percentage points higher than those without prostate cancer. However, there was no relationship of EPA and DHA to low-grade, less aggressive types of prostate cancer. Based on this result, the authors cautioned men about using fish oil or eating fish, although they state that these results do not have any direct bearing on what men with prostate cancer should do.
The practice of linking blood levels of some natural chemical or physiological variable to later disease risk is widely used in epidemiology, and while it is not considered conclusive in linking disease risk to the natural chemical, it is considered to be a useful piece of information that may – or may not -- alert us to a real relationship. Second, it’s not surprising that the patients with prostate cancer had elevated risk factors for it (at the Block Center, we recommend that anyone at an increased risk of cancer be on an individually tailored prevention regimen). Third, the problem with lack of dietary data is truly significant. The literature on fish consumption and prostate cancer has major studies suggesting that high fish intakes are associated with lower prostate cancer risk – although there are some others that suggest no association, and yes, there have been some that suggest high fish intake is associated with higher prostate cancer risk. However, as I’ll explain below, there are mitigating factors in these studies that suggest the fish itself may not be the problem. Fourth, the analysis by Brasky et al relies on a blood measurement that has its limitations. But as I will detail later in this blog, there are other studies that have found somewhat similar results using different methods of analyzing EPA and DHA levels. Nevertheless the idea that fish consumption increases prostate cancer risk is still questionable. Intriguingly, though, these studies do point out a few cautions about fish consumption and fish oil supplements that may be helpful in prostate cancer prevention.
To summarize, the study by Brasky and colleagues finds a statistical association between relatively elevated (but still rather low) levels of EPA and DHA, which come from fish, and high-grade prostate cancer. Because of the numerous limitations and flaws in the study’s methodology that I just reviewed, all the study can really do is suggest a possible correlation that needs substantially more investigation before we can rely on it to make any choices about diet and supplementation. In addition, it is important to remember that the majority of studies, some with considerable rigor, demonstrate both fish and fish oil as a beneficial prevention therapy.
Tomorrow’s blog will take a look at some interesting findings from other studies that looked at fish consumption and prostate cancer, as well as delve into the background of this study, which also uncovered some interesting findings about fish and prostate cancer.
Comments