Should You Eat or Avoid Fish During Cancer Treatment?
Most dietitians, nutritionists, and health advocates consider fish as a healthy part of our diet, with benefits ranging from fighting inflammation to preventing heart disease and even cancer.1 Many individuals try to achieve the same benefits without consuming the fish by taking fish oil. In fact, up to 20% of cancer patients use fish oil supplements during their treatment.2
Yet, is this in the best interest of the cancer patient undergoing treatment?
The Mice Studies
As is often the case with studies on diet and nutrition, we must first turn to the mice studies. Early studies revealed that two fatty acids result in the resistance of cancer cells to chemotherapy in mice — even in small quantities. The following polyunsaturated fatty acids (PUFAs) are two culprits that appear to decrease the efficacy of chemotherapy in mice undergoing treatment for cancer:
4,7,10,13-hexadecatetraenoic acid (16:4(n-3))
When patients are given chemotherapy drugs, they are toxic to both cancer cells and normal cells. This unwanted damage is necessary to provide a lethal blow to the cancer cells as they replicate. Any decrease in this damage could potentially decrease the cancer cell-killing ability of the chemo. These fatty acids are apparently released by our normal cells to help protect us from this damage, yet, this may also benefit cancer cells.
Scientists have tried to block the release of these fatty acids in order to increase the DNA-damaging effects of chemotherapy by blocking splenic cells with a drug or by removing the spleen (one of the sources of these fatty acids).3 They even found that when cancer cells are given one of these two fatty acids along with chemotherapy, there was a decrease in a marker that signifies DNA damage, known as γH2AX.
Taken together, the clinical significance of these fatty acids is unknown, but this data simply suggests that these substances could potentially offset the lethal effects of chemotherapy on cancer cells. This, of course, is a serious concern for the cancer patient receiving treatment.
The same group again identified two fatty acids released from our mesenchymal cells in the face of chemotherapy treatment that protect cancer cells from the damage:4
12-oxo-5,8,10-heptadecatrienoic acid (KHT)
hexadeca-4,7,10,13-tetraenoic acid (16:4(n-3))
These two PUFAs are the same or derivatives of the PUFAs listed above in the first study. This study also holds importance as it appears that cancer cells may recruit these mesenchymal cells to aid in their growth and proliferation.5
They again showed that, much like with the spleen, blocking the release of these fatty acids can help halt this resistance to chemotherapy. This was done by blocking cyclooxygenase-1 and thromboxane synthase, which are enzymes that help produce these two fats and part of the infamous COX pathway that is affected by nonsteroidal anti-inflammatory drugs like aspirin and ibuprofen.
The authors then showed that 16:4(n-3) became significantly elevated in patients with esophageal cancer just hours after they were given the chemotherapeutic agent cisplatin. While the release of this fatty acid is likely our body’s natural and healthy response to the introduction of a toxic substance, this may be unwanted when trying to increase toxicity to help kill cancer cells.
A Fishy Conclusion?
The 16:4(n-3) PUFA mentioned above is present in large amounts in fish oil pills and algae extract. The authors state that this is quite concerning, as many cancer patients take these supplements. Their tumor models even showed that when mice were fed fish oil and algae extracts, it offset the tumor-killing effects of cisplatin — and this was in amounts similar to daily recommended doses for humans.
This group has concluded that the use of fish oil products and algae should be avoided during chemotherapy. Others are not so convinced by this data and have referred to their conclusions as “fishy,” due to the plethora of research revealing the many potential benefits of fish oil, from preventing cachexia (weight/muscle loss and inflammation), tumor growth, and side effects of chemotherapy.6
Fish Oil Consumption and the Rise of Chemotherapy-Altering Fatty Acids
This group from the Netherlands most recently extended their initial findings to humans by studying the response to these supplements when consumed by non-cancer patients. First off, they found that 16:4(n-3) is present in fish oil tablets, ranging from 0.2 to 5.7 µM. Compare this with the mouse experiments above, which showed that the addition of 1 µL of fish oil to cisplatin resulted in resistance to this chemotherapy.
Volunteers were then given several different fishy cocktails, including:
A single dose of 10 or 50 mL of three commercially available fish oils
100g of raw salmon or tuna, smoked mackerel, or cured herring
The fish oil tablets were produced from anchovies and sardines to standardize the fatty acid components, but contained variable levels of 16:4(n-3). The fish came from a local market. Over the next two weeks, blood was collected from the participants before fish oil ingestion, and then one-half, one, two, four, six, and eight hours afterwards.
As expected, the fish oil caused a significant rise in blood 16:4(n-3), rising from a baseline of 11.4 nM to up to 400 nM with the 50 mL dose. The peak appeared to be four hours after ingestion and complete normalization occurred eight hours after ingestion of the 10 mL dose, though levels remained elevated for eight hours after the 50 mL dose.
Based on these results, they next assessed serum rises in 16:4(n-3) after the consumption of fish. Mackerel and herring contain higher amounts of this fatty acid than salmon or tuna. Accordingly, consumption of the mackerel and herring resulted in significant increases in plasma levels of 16:4(n-3), though short-lived, while salmon resulted in a brief spike and tuna had little effect.
The authors now recommend avoiding fish oil supplements the day before, the day of, and the day after chemotherapy. They also cautioned against eating mackerel or herring, which are fatty fish, as they also increase the serum amount of this fatty acid, though only briefly.
While these studies are compelling, the tell-tale method for a definitive answer would of course be a randomized trial, where half of patients receiving chemotherapy purposefully ate fish or fish oil around treatment time and half did not. The lead author feels that the data is so compelling that such a study would be unethical.
Until we have more answers, it seems that simply avoiding fish oil in the diet directly around the time of chemotherapy treatment is reasonable. While there is no data as of yet, it may be assumed that the same holds true for radiation therapy.
I would perhaps suggest the complete elimination of fish oil during treatment with radiation therapy, as this generally takes place every Monday through Friday for weeks at a time. Fish oil tablets are also not standardized, thus oftentimes patients are not even sure what they are taking. Fish in the diet can simply be moved around to avoid overlap, as the elevations are short-lived.
One final interesting aspect of this study is the acceptance of the potential effect that food can have on cancer treatment. This has been an area in cancer care that has been relatively neglected, yet a plethora of data continues to accumulate and reveal the vital link between diet and cancer.
To Your Health,
Dr. Colin Champ
Dr. Colin Champ is a practicing radiation oncologist and nutritional expert. He is the author of Misguided Medicine: The truth behind ill-advised medical recommendations and how to take health back into your hands” You can hear more from him as the host of the incredibly popular Caveman Doctor podcast.
1. Simopoulos AP. Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases. J Am Coll Nutr. 2002;21(6):495-505. http://www.jacn.org/content/21/6/495.abstract.
2. Gupta D, Lis CG, Birdsall TC, Grutsch JF. The use of dietary supplements in a community hospital comprehensive cancer center: implications for conventional cancer care. Support Care Cancer. 2005;13(11):912-919. doi:10.1007/s00520-005-0820-9.
3. Houthuijzen JM, Daenen LGM, Roodhart JML, et al. Lysophospholipids secreted by splenic macrophages induce chemotherapy resistance via interference with the DNA damage response. Nat Commun. 2014;5:5275. doi:10.1038/ncomms6275.
4. Roodhart JML, Daenen LGM, Stigter ECA, et al. Mesenchymal stem cells induce resistance to chemotherapy through the release of platinum-induced fatty acids. Cancer Cell. 2011;20(3):370-383. doi:10.1016/j.ccr.2011.08.010.
5. Jain RK, Duda DG. Role of bone marrow-derived cells in tumor angiogenesis and treatment. Cancer Cell. 2003;3(6):515-516. doi:10.1016/S1535-6108(03)00138-7.
6. Murphy RA, Clandinin MT, Chu QS, Arends J, Mazurak VC. A fishy conclusion regarding n-3 fatty acid supplementation in cancer patients. Clin Nutr. 2013;32(3):466-467. doi:10.1016/j.clnu.2012.05.013.