Anthony D’Amico, MD, PhD, professor, department of radiation oncology, Harvard Medical School, and chief, genitourinary radiation oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, all in Boston.
Cardiovascular disease, arthritis, Alzheimer’s disease, depression, fatigue, psoriasis and bedsores. What do all these conditions have in common? All can be helped by omega-3 fatty acids, the healthful fats found in fish and certain other foods. The benefits of omega-3s have been proven over and over again, which explains why fish oil is one of the most commonly used supplements in the US, following only multivitamins and calcium.
That’s why many people were shocked, disappointed, appalled or even angry when a recent study in Journal of the National Cancer Institute called omega-3s’ benefits into question by showing that men who had higher blood levels of these long-chain fatty acids had a greater chance of developing prostate cancer, especially the more dangerous, aggressive form of the disease.
That news set off a firestorm, with some articles and interviewers in the media taking leaps and reaching conclusions that weren’t suggested by the study. With so much dissention swirling about in the media and medical community, it’s no wonder that many men are confused. So to help separate the facts from the hysteria, we looked very closely at the study behind the controversy.
Most importantly, this latest study does not prove that eating fish or taking fish oil supplements causes cancer. It only shows an association between high blood levels of certain fatty acids and increased risk for prostate cancer.
This study was piggybacked onto an earlier study that was designed to see whether selenium and/or vitamin E would protect against prostate cancer. In the largest-ever prostate cancer prevention trial, more than 35,000 men were randomly assigned to take one, both or neither of those nutrients. (Note that fish oil supplements were not among the supplements tested.) In the following years, however, it became clear that prostate cancer rates were not lower among men taking selenium or vitamin E…and in fact, researchers determined that vitamin E actually increased prostate cancer risk.
All the information about these study participants, including their blood samples, was available for analysis, so researchers at Fred Hutchinson Cancer Research Center in Seattle took advantage of the data. Among the participants, they found 834 men who had gone on to develop prostate cancer, of which 156 were high-grade (advanced) disease. The researchers then looked closely at the types of fats in the blood samples that had been taken from the men at the start of the original trial.
Startling finding: Compared with men who had the lowest blood levels of the omega-3 fatty acids found in fish—eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA)—men with the highest blood levels had a 43% greater chance of developing prostate cancer…and a 71% greater chance of developing the most dangerous and aggressive form of the disease.
The researchers also measured blood levels of alpha-linolenic acid, a plant-based omega-3 found in flaxseed, soy and walnuts. It was not associated with increased prostate cancer risk, and neither were omega-6 fatty acids or trans fats.
The results of the study were surprising, even to the lead author, Theodore Brasky, PhD. He wasn’t caught completely off guard, however, because an earlier study of his involving a different group of men had had the same basic results.
Debate sparked: When news of this study hit the media, many people expressed serious skepticism about the validity of the findings. That’s a good thing—constructive dialog among experts leads to questions that often can be addressed in future studies, furthering our scientific knowledge overall. Below are objections that have been raised about the study and what we found when we investigated them.
Among those questioning the study was Anthony D’Amico, MD, PhD, a Harvard Medical School professor and radiation oncologist. He was concerned, he said, about whether the study researchers had adequately controlled for all of the other factors known to increase prostate cancer risk. Blaming high omega-3 levels for prostate cancer without controlling for other risk factors would be bad science—and could lead to unjustly blaming “innocent bystander” omega-3s while ignoring the true culprit.
Those other risk factors include family history of prostate cancer…increasing age…elevated blood levels of prostate-specific antigen (PSA), a protein produced by the prostate gland that is often elevated in men with prostate cancer…black race…results of a rectal exam to check for enlarged prostate…and diabetes.
So the question is, did the study researchers take all these risk factors into account? As it turns out, yes. At the start of the study, none of the men’s rectal exams were abnormal, and the researchers did adjust for family history of prostate cancer and for diabetes. Also, in making their comparisons, the researchers matched the men who developed prostate cancer with those who did not by both age and racial group, Dr. Brasky said. At the start of the study, all participants were put into subgroups based on age and race. Because black men in general face a significantly higher risk for prostate cancer than men of other races, analysis of their data was kept separate. For example, a 75-year-old black man was not compared with a 60-year-old white man, but only with other black men in the same age bracket.
As for PSA, all the men had normal PSA levels at the start of the study when the blood was first collected, which was done up to nine years before anyone was diagnosed with prostate cancer. However, Dr. D’Amico pointed out that increasing PSA levels are a risk factor for aggressive prostate cancer—and the study indeed was not designed to detect such increases.
Dr. Brasky contended, though, that it’s possible that omega-3s affect PSA, and that PSA in turn affects cancer risk—which means it would be inappropriate to adjust for PSA levels. In addition, he said, his team “made several attempts to adjust for the timing of the last prostate cancer screening, which is less problematic in terms of adjustment, and there was no meaningful change in the results.”
Some people who faulted the study suggested that men might have rushed to take fish oil after they were diagnosed with prostate cancer in an attempt to make themselves healthier. However, that was not the case. All the men in the study had normal rectal exams, normal PSA levels and no history of prostate cancer at the time their blood samples were drawn—so they did not yet have a cancer diagnosis to motivate them to take fish oil supplements, eat more fish or make other dietary changes.
As a group, the men who ultimately developed prostate cancer did tend to have more relatives with prostate cancer and higher education—so it is plausible that these men might have started taking fish oil supplements proactively in an attempt to prevent prostate cancer. If that’s the case, then the higher omega-3 levels were actually a result of perceived increased risk rather than a suspected cause of increased risk. However, this effect was likely negligible, given that the researchers did adjust for both family history and education level.
The men who ended up with prostate cancer also tended to have slightly higher baseline PSA levels. Since their PSA test results were all within the normal range, though, Dr. Brasky thought it unlikely that these men would have tried to protect themselves against cancer by eating more fish or taking fish oil supplements in the time between the PSA test and the baseline blood draw used for the analysis of the fatty acids.
Some critics say that the study just doesn’t make sense, given that prostate cancer rates are much lower in parts of the world where people generally eat a lot more fish than Americans do. For instance in Asia, where fish consumption is high, the prostate cancer rate is very low.
However, a separate study of Japanese men has shown that those who ate fish more than four times a week had a prostate cancer risk more than 50% higher than men who ate fish less than twice a week.
We also should acknowledge that the factors driving geographic and/or ethnic differences in cancer rates are quite complicated. For instance, here in the US, men from different ethnic groups have quite different levels of risk for prostate cancer, with the rate among black men (the highest) being nearly three times the rate among Native Americans and Alaskan natives (the lowest). What drives those differences isn’t easy to determine. It’s likely that genetic and environmental factors—not just dietary factors—play some role in the difference.
So we cannot assume that omega-3s protect against prostate cancer simply because Asian men eat lots of fish and their prostate cancer risk is low. After all, Scandinavian men eat lots of fish, too, and their prostate cancer rate is relatively high.
Another objection raised about the study was that it did not identify the source of the participants’ fatty acids—for instance, whether they got their omega-3s from taking fish oil supplements, eating fish or eating something else.
But: Food frequency questionnaires, which ask about consumption of certain foods and supplements, are notoriously inaccurate. Most people can’t recall specifically what they ate when, and they frequently misjudge serving sizes. For that reason, many experts say that measuring blood levels of nutrients, as the researchers did in this study, is actually a far more reliable indicator of a person’s nutritional status.
That said, questions do remain about the types of fish and other omega-3-rich foods that the participants ate…and about the types of fish oil supplements they may have taken. For instance, fish and fish oil pills could contain contaminants—mercury, PCBs or something else we don’t yet know about—that might be the true culprits behind any association between omega-3s and prostate cancer. While existing studies on mercury exposure and prostate cancer have shown mixed results, with most large studies showing little or no risk, we can’t dismiss the possibility that some type of contaminant in fish, rather than the omega-3s themselves, are to blame.
Critics of the study also questioned the significance of the omega-3 blood levels. Reason: After a person eats fish or takes a fish oil pill, his blood levels of free fatty acids rise and stay elevated for four to 12 hours, but then go back down within about 48 hours as the fatty acids leave his system. So the omega-3 levels in the men’s blood samples represented just a certain moment in time and did not necessarily accurately represent the participants’ long-term diet or supplement habits.
To that objection, Dr. Brasky said, “This is not as problematic as it sounds. Yes, there is always a concern that a single blood draw is not representative of habitual diet. However, plasma phospholipid fatty acids (versus free fatty acids) are reasonably correlated with dietary intake and are reflective of weeks to about a month of diet”—and those phospholipid fatty acids are what the researchers measured. It’s also worth noting that this same situation applies to all epidemiologic studies that use blood biomarkers of fatty acids to assess the risk of any disease—heart disease, breast cancer, etc.—and so it is not at all unique to this particular study.
Some skeptics suggest that certain studies are funded by pharmaceutical companies whose money-driven agenda is to discredit the nutritional supplement industry in order to increase the market for their drugs. Be that as it may, it’s not the case in this study—because the funding came from the National Center for Complementary and Alternative Medicine and the National Cancer Institute.
Other critics of the study point to Dr. Brasky’s earlier research on omega-3 fatty acids and prostate cancer as evidence that he is pushing an “anti-supplement” agenda. And it didn’t help that another of the study authors was quoted in the study center’s own press release as saying, “We’ve shown once again that use of nutritional supplements may be harmful.”
But: Dr. Brasky, an epidemiologist who studies the effects of inflammation on cancer, also published a study with findings that were favorable toward supplements, showing that fish oil supplementation was associated with reduced risk for breast cancer.
He was just as surprised and disappointed as everyone else the first time he found the link between omega-3s and increased prostate cancer risk, Dr. Brasky told us. He had expected that omega-3s would have a protective effect, given that they are anti-inflammatory and that other inflammation-fighters, such as aspirin, have been shown to reduce prostate cancer risk in animals and people. “When the results of our studies showed the opposite effect, meaning more cancer rather than less, those findings were most definitely not celebrated in our lab,” Dr. Brasky said.
Prostate cancer is the leading cancer for men, and there will be approximately 238,600 new cases diagnosed in the US in 2013. Though fewer than 10% of those cancers will be the most dangerous aggressive type, the disease kills nearly 30,000 American men each year.
To put that in perspective, though, heart disease kills nearly 600,000 American men each year—and a lot of research suggests that omega-3s are beneficial in helping prevent heart disease. Even if what is good for the heart is bad for the prostate, we’re left to ponder the balance between omega-3s’ pros and cons.
So what’s a man to do? “I would not tell people that eating fish or taking fish oil supplements is dangerous. There isn’t anything in the study proving that fish or fish oil causes prostate cancer—and we know that omega-3s help the heart,” Dr. D’Amico said.
A wise move would be for men to discuss their own personal situations with their physicians. For instance, a man with excellent heart health but a strong family history of prostate cancer might be advised to avoid fish oil supplements and limit fish consumption while otherwise following an anti-inflammatory diet. However, a man with no signs of prostate trouble but multiple risk factors for heart disease might be counseled to continue eating fish and taking fish oil pills.
As for how much omega-3 might be too much, Dr. Brasky’s study did not look at the question in those terms. However, in his study the difference in omega-3 blood levels between the highest-risk group and the lowest-risk group was not very large—it was about the difference you’d expect to see if the highest-risk group ate two more servings of salmon per week than the lowest-risk group.
Interestingly, that’s in line with an earlier study that we covered here at Daily Health News. It showed that eating just two servings of fish per week—for an average omega-3 intake of approximately 400 mg per day or 2,800 mg per week—provided enough of the essential fatty acids to reduce the risk of dying from any cause, while eating more than two servings did not provide any additional benefit. So until additional studies provide clearer answers, your doctor may advise you that, when it comes to omega-3s—as with most things in life—moderation is generally the best policy.