alanbarlee Posted April 3, 2015 Share Posted April 3, 2015 This recent Dutch study raises an important precaution for people undergoing chemotherapy while consuming oily fish or fish oil supplements. The serum-elevating effect of ingesting tiny amounts of a particular fatty acid component was measured both in mice and in humans, but the study necessarily used mouse models for measuring the induced chemo resistance that the fatty acid appears to cause. The investigation of this fatty acid component into stopping the normal tumour response to chemotherapy was limited to cis-platin and oxaliplatin, which are different agents to those commonly used for treating metastatic prostate cancer, viz docetaxel and cabazitaxel. However, the Dutch rcommendation to avoid oily fish and fish oil prior for up to two days prior to and after infusion sounds like a useful precaution for all chemotherapy, pending further studies with non-platin agents. Alan Increased Plasma Levels of Chemoresistance-Inducing Fatty Acid 16:4(n-3) After Consumption of Fish and Fish Oil Laura G. M. Daenen, MD, PhD1; Geert A. Cirkel, MD1; Julia M. Houthuijzen, MSc2; Johan Gerrits, BSc3; Ilse Oosterom, MSc1; Jeanine M. L. Roodhart, MD, PhD1; Harm van Tinteren, PhD4; Kenji Ishihara, PhD5; Alwin D. R. Huitema, PharmD6; Nanda M. Verhoeven-Duif, PhD3; Emile E. Voest, MD, PhD1,2 [+] Author Affiliations JAMA Oncol. Published online April 02, 2015. doi:10.1001/jamaoncol.2015.0388 ABSTRACT Importance Our research group previously identified specific endogenous platinum-induced fatty acids (PIFAs) that, in picomolar quantities, activate splenic macrophages leading to resistance to chemotherapy in mouse models. Fish oil was shown to contain the PIFA 16:4(n-3) (hexadeca-4,7,10,13-tetraenoic acid) and when administered to mice neutralized chemotherapy activity. Objective Because patients with cancer frequently use fish oil supplements, we set out to determine exposure to 16:4(n-3) after intake of fish or fish oil. Design, Setting, and Participants (1) In November 2011, 400 patients with cancer undergoing treatment at the University Medical Center Utrecht were surveyed to determine their use of fish oil supplements; 118 patients responded to the questionnaire (30%); (2) pharmacokinetic analysis of the 16:4(n-3) content of 6 fish oils and 4 fishes was carried out; (3) from April through November 2012, a healthy volunteer study was performed to determine 16:4(n-3) plasma levels after intake of 3 different brands of fish oil or 4 different fish species. Thirty healthy volunteers were randomly selected for the fish oil study; 20 were randomly selected for the fish study. These studies were supported by preclinical tumor experiments in mice to determine chemoresistance conducted between September 2011 and December 2012. Primary Outcomes and Measures (1) Rate of use of fish oil supplements among patients undergoing cancer treatment at our institution; (2) levels of 16:4(n-3) present in 3 brands of fish oil and 4 species of fish; and (3) plasma levels of 16:4(n-3) present in healthy volunteers after consuming fish oil or fish. Results Eleven percent of respondents reported using omega-3 supplements. All fish oils tested contained relevant amounts of 16:4(n-3), from 0.2 to 5.7 µM. Mouse experiments showed that addition of 1 µL of fish oil to cisplatin was sufficient to induce chemoresistance, treatment having no impact on the growth rate of tumors compared with vehicle-treated controls (estimated tumor volume difference, 44.1 mm3; P > .99). When the recommended daily amount of 10 mL of fish oil was administered to healthy volunteers, rises in plasma 16:4(n-3) levels were observed, reaching up to 20 times the baseline levels. Herring and mackerel contained high levels of 16:4(n-3) in contrast to salmon and tuna. Consumption of fish with high levels of 16:4(n-3) also resulted in elevated plasma levels of 16:4(n-3). Conclusions and Relevance All tested fish oils and herring and mackerel fishes contained relevant levels of fatty acid 16:4(n-3), a fatty acid with chemotherapy-negating effects in preclinical models. After ingestion of these fish oils or fishes, 16:4(n-3) was rapidly taken up in the plasma of human volunteers. Until further data become available, fish oil and fish containing high levels of 16:4(n-3) may best be avoided on the days surrounding chemotherapy. Taken together, our findings are in line with a growing awareness of the biological activity of various fatty acids and their receptors and raise concern about the simultaneous use of chemotherapy and fish oil. Based on our findings, and until further data become available, we advise patients to temporarily avoid fish oil from the day before chemotherapy until the day thereafter. This advice was adopted by the Dutch Cancer Society, and by the Dutch National Working Group for Oncologic Dieticians. Although further evidence on the relation between fish consumption and chemotherapy activity is desired, we would currently also recommend to avoid herring and mackerel in the 48 hours surrounding chemotherapy exposure. Link to comment Share on other sites More sharing options...
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