In 2011, it was reported that two fatty acids (12-oxo-5,8,10-heptadecatrienoic acid and hexadeca-4,7,10,13-tetraenoic acid) found in some fish oil supplements can induce resistance to platinum-based chemotherapy drugs, even if present only in minute quantities. It was demonstrated that animals administered "normal amounts" of fish oil containing the fatty acids became insensitive to chemotherapy.
Now the authors have published a new study in which they confirm that consuming fish oil supplements, herring or mackerel could neutralize the treatment effects of platinum-based chemotherapy such as cisplatin.
Marine fatty acids
Fatty acids are components of lipids. Broadly speaking, lipids are types of fats, including oils, waxes, hormones, fat-soluble vitamins, triglycerides, and others. Lipids form an important part of cell membranes. Lipids normally are made up of fatty acids plus other molecules. For example, triglycerides consist of three fatty acids bonded with glycerol. Omega-3 marine fatty acids are found primarily in fatty fish, marine algae and shellfish. The most important are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, each serving of these foods normally contains multiple types of fatty acids in various proportions.
Relatively high fatty fish intake has been shown to be associated with reduced risk of breast cancer and improved survival. In one experiment, higher omega-3 to omega-6 fatty acid diets reduced mammary gland density, which in turn reduced carcinogen-induced mammary tumor development. Fish oil has been shown to inhibit early stages of mammary tumor development in a mouse model of HER-2/neu overexpressing (HER2+) breast cancer. DHA has been demonstrated to reduce bone metastasis in a mouse model of breast cancer. Marine fatty acids have also been found to enhance the therapeutic effects of what to eat during tamoxifen treatment and chemotherapy drugs such as Adriamycin and Taxol.
Latest research finds fish oil, herring or mackerel could hinder chemotherapy
The study referenced at the beginning of this news story was designed to determine exposure to the fatty acid hexadeca-4,7,10,13-tetraenoic acid (16:4(n-3)) after consumption of fish or fish oil supplements. The study consisted of three separate parts: (1) determine the use of fish oil supplements among patients undergoing cancer treatment at the University Medical Center in Utrecht, Netherlands; (2) determine levels of 16:4(n-3) in three brands of fish oil and four species of fish; and (3) determine circulating levels of 16:4(n-3) in healthy subjects after consuming fish oil or fish. The authors also performed experiments in mice to determine the degree of chemoresistance caused by 16:4(n-3). Addition of 1 µL of fish oil during cisplatin treatment was sufficient to induce chemoresistance—treatment had no impact on the growth rate of tumors in the presence of the associated 16:4(n-3).
Part 1: 400 cancer patients treated at the University Medical Center Utrecht (Netherlands) were sent a questionnaire in November 2011 to determine their use of fish oil supplements. A total of 118 patients (30%) responded to the questionnaire, of whom 13 (11%) reported using omega-3 supplements.
Part 2: Levels of 16:4(n-3) content of six fish oils and four different fish were determined. All the fish oils contained 16:4(n-3) in amounts likely to cause chemoresistance, from 0.2 to 5.7 µM. Herring and mackerel were also found to contain high levels of 16:4(n-3), in contrast to insignificant levels in salmon and tuna.
Part 3: Healthy volunteers were tested to determine plasma levels of 16:4(n-3) after consuming three different brands of fish oil supplements or four different fish species. Thirty healthy volunteers participated in the fish oil study; 20 were in the fish study. Increases in plasma 16:4(n-3) levels, reaching up to 20 times baseline levels, were observed when the recommended daily amount of 1,000 mg of fish oil was given to healthy volunteers. Levels of 16:4(n-3) returned to close to normal eight hours after a 1,000 mg dose of fish oil dose was ingested; a 5,000 mg dose resulted in more prolonged elevation. Consumption of 100 grams of herring or mackerel also resulted in elevated plasma levels of 16:4(n-3), whereas tuna did not affect blood levels, and salmon resulted in a small, short-lived peak.
The authors comment that 16:4(n-3) in amounts sufficient to neutralize the treatment effects of chemotherapy is rapidly taken up in the blood after ingestion of fish oil supplements, herring or mackerel. Until further data become available, the authors recommend that fish oil and fish containing high levels of 16:4(n-3) be avoided on the day immediately before chemotherapy through the day after chemotherapy.
Please see our article on how to optimize your breast cancer diet for information on what to eat during all stages of treatment and recovery.
Selected breast cancer studies
Abstract 3691: Fish oil increases immune cell infiltration of tumors and reduces the incidence of mammary carcinogenesis in Her2neu mice.
Turbitt WJ, Collins SD, Xu H, Washington S, Aliaga C, El-Bayoumy K, et al. Abstract 3691: Fish oil increases immune cell infiltration of tumors and reduces the incidence of mammary carcinogenesis in Her2neu mice.. Prevention Research. American Association for Cancer Research; 2013; 10.1158/1538-7445.am2013-3691
Combination of Intermittent Calorie Restriction and Eicosapentaenoic Acid for Inhibition of Mammary Tumors
Mizuno NK, Rogozina OP, Seppanen CM, Liao DJ, Cleary MP, Grossmann ME. Combination of Intermittent Calorie Restriction and Eicosapentaenoic Acid for Inhibition of Mammary Tumors. Cancer Prevention Research. American Association for Cancer Research (AACR); 2013; 6:540-547 10.1158/1940-6207.capr-13-0033
Fish Oil Alters Tamoxifen-Modulated Expression of mRNAs That Encode Genes Related to Differentiation, Proliferation, Metastasis, and Immune Response in Rat Mammary Tumors
Bidinotto LT, Cicco RLd, Vanegas JE, Santucci-Pereira J, Heuvel JPV, Washington S, et al. Fish Oil Alters Tamoxifen-Modulated Expression of mRNAs That Encode Genes Related to Differentiation, Proliferation, Metastasis, and Immune Response in Rat Mammary Tumors. Nutrition and Cancer. Informa UK Limited; 2012; 64:991-999 10.1080/01635581.2012.712736
Dietary Omega-3 Supplementation Exacerbates Left Ventricular Dysfunction in an Ovine Model of Anthracycline-Induced Cardiotoxicity
Carbone A, Psaltis PJ, Nelson AJ, Metcalf R, Richardson JD, Weightman M, et al. Dietary Omega-3 Supplementation Exacerbates Left Ventricular Dysfunction in an Ovine Model of Anthracycline-Induced Cardiotoxicity. Journal of Cardiac Failure. Elsevier BV; 2012; 18:502-511 10.1016/j.cardfail.2012.03.005
Abstract 585: Eicosapentaenoic acid increases mammary tumor inhibition of intermittent calorie restriction and regulates adipokines
Mizuno NK, Rogozina OP, Seppanen CM, Liao DJ, Cleary MP, Grossmann ME. Abstract 585: Eicosapentaenoic acid increases mammary tumor inhibition of intermittent calorie restriction and regulates adipokines. Prevention Research. American Association for Cancer Research; 2012; 10.1158/1538-7445.am2012-585
Mesenchymal Stem Cells Induce Resistance to Chemotherapy through the Release of Platinum-Induced Fatty Acids
Roodhart J, Daenen L, Stigter E, Prins H, Gerrits J, Houthuijzen J, et al. Mesenchymal Stem Cells Induce Resistance to Chemotherapy through the Release of Platinum-Induced Fatty Acids. Cancer Cell. Elsevier BV; 2011; 20:370-383 10.1016/j.ccr.2011.08.010