A major story on health news websites last week was a study from the Netherlands suggesting that fish oil will negate the effects of cancer chemotherapy. This study was published in JAMA Oncology, and thus attracted much attention. It’s actually a continuation of a study that we blogged about a few years ago: https://lifeovercancer.wordpress.com/2011/09/27/fish-oil-and-chemotherapy-the-bigger-picture/. We’ll get into the details of the study in a moment, but because the stories that circulated about this study may have prompted concern among cancer patients using fish oil, we want to offer some reassurance. There are, in fact, a large number of studies that suggest that fish oil and its constituents – EPA and DHA – actually increase, rather than decrease, the sensitivity of cancer cells and tumors to chemotherapy, without increasing drug effects on normal cells. We will provide additional information about these studies below. However, if patients find the results of this recent study concerning, it’s not unreasonable to stop using fish oil for 48 hours, including the day before and the day of chemotherapy, as the researchers of this study suggested. It’s also a good idea for patients to discuss any concerns they may have with their treating physician.
Now, back to this study.
Fatty acids are chemical constituents of oils, like the well-known oleic acid, a constituent of olive oil. The Dutch researchers, led by Dr Emile Voerst, discovered fatty acids that suppress the action of chemotherapy on cancer cells. They called these fatty acids PIFA’s, platinum-induced fatty acids, because they were made by immune cells when they were exposed to platinum-containing drugs like cisplatin or oxaliplatin. One of these, hexadecatetraenoic acid (HTT), is found in some fish and fish oils, as well as certain algae – a concern since some algae are used as vegetarian sources of omega-3 fatty acids. This fatty acid exists at much lower levels than the better-known fish oil constituents EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Although earlier studies by the Dutch group verified the effect of HTT in reducing chemosensitivity, there were still some open questions about the mechanics and relevance of the effect.
The new study set out to answer these questions. First, the researchers examined which fish and fish oils contained HTT. The chief types of fish that contain HTT are herring, sardines and mackerel (salmon and tuna are lower in HTT than other types of fish). Though only small amounts of HTT enter the blood when someone eats these kinds of fish or takes fish oil, it’s still a concern since only small amounts were needed to affect chemotherapy drugs in this study. Importantly, HTT appeared to be excreted from the bloodstream about 8 hours after ingestion. The researchers gave commercial fish oil high in HTT to mice with implanted tumors at the same time as they gave chemo drugs, and found that even in fairly low dosages the fish oil decreased sensitivity to chemotherapy. Based on their findings, the researchers suggest that patients who use fish oil stop it for 48 hours, including the day before chemotherapy and the day of chemo (as we mentioned above). They also suggested avoiding fatty fish if patients want to eat fish during that time.
This is a fairly conservative recommendation, one we’re not convinced is necessary. Again, there are a large number of studies that suggest that fish oil, and EPA and DHA, actually increase, rather than decrease, the sensitivity of cancer cells and tumors to chemotherapy, without increasing drug effects on normal cells. These studies include a wide variety of cancers and a substantial number of cancer drugs, including targeted therapies. Many of the studies used very high doses of fish oil, which might also deliver high doses of HTT, though perhaps in these studies the large doses also delivered high enough doses of EPA and DHA to counteract any effects of the HTT.
Here are a few examples of some of these studies:
1). Fish oil from menhaden, a member of the herring family, inhibited the growth of neuroblastoma tumors implanted in mice when given by itself. When given along with Sutent, a targeted therapy, tumor growth was further inhibited, as was the growth of tumor blood vessels.
2). Fish oil fed to rats that also received a tumor-causing chemical resulted in more normal blood vessels than in rats given the same chemical without fish oil. This led to better circulation of blood, and presumably, chemotherapy, in the tumors. The fish-oil fed rats had a better response to the chemotherapy drug Taxotere.
3). EPA increased the sensitivity of colon cancer tumor cells and stem cells to the drugs 5-FU and oxaliplatin. An animal study with colon tumors caused by a carcinogenic chemical also found that the combination of fish oil and 5-FU reduced tumor growth.
4). Fish oil in the diet of mice with implanted breast cancers appears to have a pro-oxidant effect in the tumors. This sensitized them to the effects of doxorubicin, one of the chemo drugs used for breast cancer.
DHA may be even more important than EPA in sensitizing tumors to chemotherapy. It has several important mechanisms that could increase chemosensitivity. These include pro-oxidant effects, making cell membranes more permeable to drugs, and activating apoptosis (programmed cell death). It also appears to decrease metastasis by tumors.
More importantly, there are some human studies that indicate a potential positive effect of fish oil given with chemotherapy. A 2009 study gave DHA to breast cancer patients with metastases to organs like the liver. 44% of these patients had tumor shrinkage. In the patients whose plasma levels of DHA were the highest, survival time was 14 months longer than the entire population, suggesting that higher doses of DHA might useful. A 2011 randomized study gave fish oil to lung cancer patients going through chemotherapy and found that 60% of the patients who received fish oil experienced tumor shrinkage, versus only 25% of the patients who did not receive fish oil. While these studies are small, they stand in contrast to the results of the Dutch research group. Why this new study found results so different from past studies of fish oil and chemotherapy is not certain. It may have to do with dosages and types of fish oil, which would result in different amounts of EPA, DHA and HHT in the body. It may also have to do with the timing of when the fish oil was started relative to chemo treatment. Some studies have found that administering other materials with pro-oxidant effects on tumor tissues – intravenous vitamin C, for instance – increased the effects of fish oil. We do know that many studies have found positive results from testing EPA and DHA separately. This might make it beneficial to use a fish oil that is molecularly distilled, which results in higher amounts of EPA and DHA, relative to other constituents.
Whatever is behind these results, though, and whether you temporarily stop fish oil during chemo or not, it’s important to keep in mind that maintaining your intake of omega-3 fatty acids is also important. Another new study highlights this. Over 1400 breast cancer patients in Long Island, New York, were interviewed about their diets shortly after diagnosis Those who had the highest consumption of tuna, other fish that was baked or broiled, and EPA and DHA had lower mortality rates than those who had the lowest intake. The reductions were between 25% and 30%, a finding that was significant both statistically and for patients searching for ways to improve their chances in the battle with cancer.