Do Fish Oils Really Increase Prostate Cancer Risk?

salmonThousands of patients were anxiously calling their doctors last week after a new study found that fish oils might increase the risk of prostate cancer.

Published in the Journal of the National Cancer Institute, the study found that high concentrations of EPA, DPA and DHA — three fatty acids derived from omega-3-rich oily fish and fish-oil supplements — were associated with a 71% increased risk of high-grade prostate cancer. The study also noted a 44% increase in the risk of low-grade prostate cancer and an overall 43% increase in risk for all prostate cancers.

“This study has caused a lot of anxiety among patients and confusion among doctors because it flies in the face of the widespread assumption that omega-3 fats are cancer-protective,” Dr. Philippa Cheetham, Attending in Urology at Winthrop University Hospital, New York, told me in an interview. “There are a lot of studies that highlight the benefits of fish oils with regard to prostate cancer,” she said. “This study is very flawed and won’t change my practice of recommending oily fish to people with prostate cancer.”

According to Dr. Cheetham, the article was based on “a poor quality retrospective study, [when] there are many prospective studies that support the safety and efficacy of fish oils in prostate cancer prevention.” She points out that the researchers did not control for any of the known risk factors for prostate cancer, including family history and race, with African American men having a higher incidence of prostate cancer.

Further, she notes, they did not standardize the amount or quality of fish oil that patients were taking (as we explain below, some risks may be related to fish oils that are not purified) and they did not control for how long patients were taking fish oil prior to their diagnosis of prostate cancer.

“At best, this study shows a weak association, and not a cause and effect,” Dr. Cheetham concludes.

Omega-3s’ cancer-protective properties

The long-chain omega-3 fats DHA and EPA are abundant only in fish and some forms of algae. They have been found to suppress cancer initiation, induce cell apoptosis and decrease proliferation of several cancers including prostate cancer. Indeed, there is a substantial store of evidence highlighting the benefits of marine fatty acids.

For instance, a 2010 meta-analysis of fish consumption and prostate cancer reported no overall relationship between the two, but a significant reduction in late-stage or fatal cancer.

Another study in 2001 found that higher fish intake was associated with lower risk for prostate cancer incidence and death. In a group of over 6,000 Swedish men followed over 30 years, those who ate no fish had a two- to three-fold higher frequency of prostate cancer than those who ate moderate or high amounts.

In Canada, another study found that intakes of canned, preserved fish were associated with a lower risk for prostate cancer .

And in a Swedish study, those subjects who ate oily fish more than three times a week had almost half the risk of metastatic prostate cancer compared with those who ate fish less than twice a month. Each additional daily intake of 0.5 g of marine fatty acid from food was associated with a 24% decreased risk of metastatic cancer.

So what’s wrong with the latest study?

First: the study was observational in nature. This means that the researchers observed dietary patterns and disease patterns, and looked for correlations between the two. They did not set out to test the relationship between fish oils and prostate cancer (these patients were part of a study investigating vitamin E and selenium supplements, not fish oils, for the prevention of prostate cancer).

Now, as statisticians are quick to remind us: correlation is not causation. Thus, just because people with higher levels of omega-3 fatty acids in their blood also have higher prostate cancer rates, this does not necessarily mean that the fish oils are causing the cancer; there may be other factors at play that are related to fish consumption, for instance marine pollutants.

Moreover, as lipids researcher William Harris, Professor in the Department of Medicine at the University of South Dakota points, out in an article published on Lecturepad, the reported EPA and DHA blood levels in this study were 3.62% in the no-cancer control group, 3.66% in the total cancer group, 3.67% in the low grade cancer group, and 3.74% in the high-grade group.

“These differences between cases and controls are very small and would have no meaning clinically as they are within the normal variation,” Harris notes, adding: “… to conclude that regular consumption of two oily fish meals a week or taking fish oil supplements would increase risk for prostate cancer is extrapolating far beyond the data.”

In addition, Harris points out, if high dietary intake of omega-3s caused more cancer, we would expect cultures that consume lots of fish oil to have higher prostate cancer rates. However, high omega-3 intakes seem to be associated with low cancer rates. For instance, the Japanese eat eight times more omega-3 fatty acids than Americans and their blood levels are twice as high, yet the prostate cancer rates are only one-sixth the American rate. (Might this be because the Japenese mostly consume actual fish, rather than fish-oil capsules?)

The risks of oxidized fish oil

Of course, omega-3s aren’t completely benign and there are known mechanisms by which fish oils might induce or promote cancer — something the controversial new study may have picked up.

Of all fatty acids, they are the most prone to oxidation (rancidity), as health writer Paul Jaminet shows in this graph. When fish oils go rancid, they produce free radicals that can damage our cell membranes. To neutralize these, the body uses its stores of vitamin E and other antioxidants, leaving it short of many of its natural defenses and thus vulnerable to further oxidative damage.

Moreover, rancid fish oils can act as carcinogens in their own right. “Peroxidation of [polyunsaturated fatty acids] generates highly toxic compounds, such as aldehydes, which mutate DNA and turn proteins into advanced lipoxidation end products (ALEs)” Jaminet explains. Not only have these compounds been implicated as causal factors in cancer, he says; moreover, “oxidation products of DHA promote angiogenesis – the creation of new blood vessels to feed tumors. These products make cancers grow rapidly.”

What makes all this worrying is that many health conscious people take fish oil supplements daily – very often instead of eating fish. And, according to a recent paper by a team of New Zealand researchers, quite a few of the commonly available fish oil supplements may be oxidized and therefore harmful.

“When over-the-counter supplements have been investigated, the frequency of excess oxidation … was not uncommon, affecting between 11%–62% of products,” they write, concluding: “… consuming purchased supplements entails risk of exposure to unacceptably oxidized oil, and it is likely that the omega-3 supplements used in many clinical trials have also been significantly oxidized,” thus perhaps explaining the mixed outcomes of such trials.

So how can you reduce the risk of ingesting oxidized fish oils?

Contact with oxygen, heat or light can cause fish oils to oxidize, sometimes in a matter of days. So even if you buy the freshest, cleanest oils available, they can oxidize quickly in your kitchen cupboard.

According to Michael Eades MD, there are several ways to slow this process.

“First, purchase the freshest fish oil capsules you can find. Take them home, and if they are in plastic bottles, put them in glass bottles. Plastic bottles, surprisingly enough, are not totally impervious to air. Glass bottles are impervious to air. Most fish oil is encapsulated using gel caps, which are also not impervious to air. You can’t … re-encapsulate the fish oil, so you’ve got to live with the gel caps, but putting them into a glass bottle keeps the air from getting to the gel caps in the first place.”

Second, he advises, put the glass bottle in the refrigerator. The cold will markedly slow down the oxidation process even if a little air gets in the bottle. Refrigerated fish last a lot longer than fish left out on the counter.

The final step to insure the freshness of fish oil capsules is to bite into one and chew it, Dr. Eades recommends. “If it is rancid, you’ll know it. If it is, throw the whole batch out. If you perform the chew test every four or five days, you’ll always know you’re taking un-rancid fish oil. You can tell whether fish oil is oxidized by its taste.” As fish oil oxidizes, it begins to release a distinct pungent, sharp odor and unpleasantly fishy flavor.

To further lower the risks of taking potentially oxidized fish oils, Dr. Cheetham recommends using supplements that have been purified (pharmaceutical grade or molecularly distilled); that contain an antioxidant like vitamin E or rosemary oil to prevent rancidity; and that come from small, oily cold-water fish, such as anchovies or sardines.

Radical idea: Just eat fish!

A simpler and cheaper way to obtain the benefits of omega-3s without the risks is to eat oily fish and accompany it with a wide range of antioxidants found in vegetables, fruits, herbs, spices, nuts and olive oil. In short: Eat the traditional Mediterranean diet.

As many studies have shown, cancer incidence – including prostate cancer – is lower among people who eat a Mediterranean diet (for instance, see this article, this one or this one).

Indeed, the anti-cancer effects of omega-3s are greatly enhanced by such diets, rather than the typically Western diets dominated by red meat, dairy products, refined carbohydrates, hydrogenated oil, and highly unsaturated vegetable and seed oils, Dr. Cheetham says.

So rather than spend fortunes on top-of-the-line fish oil capsules and chomping on them every few days to test their non-rancidity, I recommend that you hot-foot it to your nearest fresh-fish counter, buy a nice filet of wild-caught salmon and poach it in olive oil with garlic, rosemary and lemon (see recipe in the latest issue of Everyday Mediterranean).

Alternatively, baked mackerel in mustard sauce, crunchy almond-topped broiled trout trout, sardine salad or a few canned sardines atop a mixed summer salad – recipes in Zest for Life: The Mediterranean Anti-Cancer Diet – will provide precious omega-3 fatty acids and the antioxidants to protect them from oxidation.