Increased Plasma Levels of Chemoresistance-Inducing Fatty Acid 16:4(n-3) After Consumption of Fish and Fish Oil.
JAMA Oncol
; 1(3): 350-8, 2015 Jun.
Article
en En
| MEDLINE
| ID: mdl-26181186
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 164(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 164(n-3) after intake of fish or fish oil. DESIGN, SETTING, ANDPARTICIPANTS:
(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 164(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 164(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. MAIN OUTCOMES ANDMEASURES:
(1) Rate of use of fish oil supplements among patients undergoing cancer treatment at our institution; (2) levels of 164(n-3) present in 3 brands of fish oil and 4 species of fish; and (3) plasma levels of 164(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 164(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 164(n-3) levels were observed, reaching up to 20 times the baseline levels. Herring and mackerel contained high levels of 164(n-3) in contrast to salmon and tuna. Consumption of fish with high levels of 164(n-3) also resulted in elevated plasma levels of 164(n-3). CONCLUSIONS AND RELEVANCE All tested fish oils and herring and mackerel fishes contained relevant levels of fatty acid 164(n-3), a fatty acid with chemotherapy-negating effects in preclinical models. After ingestion of these fish oils or fishes, 164(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 164(n-3) may best be avoided on the days surrounding chemotherapy.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Aceites de Pescado
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Alimentos Marinos
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Interacciones Alimento-Droga
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Resistencia a Antineoplásicos
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Suplementos Dietéticos
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Ácidos Grasos
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Peces
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Neoplasias
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Antineoplásicos
País/Región como asunto:
Europa
Idioma:
En
Revista:
JAMA Oncol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Países Bajos