RESUMEN
Observational evidence linking dietary n-3 PUFA intake and health outcomes is limited by a lack of robust validation of dietary intake using blood n-3 PUFA levels and potential confounding by fish oil supplement (FOS) use. We investigated the relationship between oily fish intake, FOS use and plasma n-3 PUFA levels in 121 650 UK Biobank (UKBB) participants. Ordinal logistic regression models, adjusted for clinical and lifestyle factors, were used to quantify the contribution of dietary oily fish intake and FOS use to plasma n-3 PUFA levels (measured by NMR spectroscopy). Oily fish intake and FOS use were reported by 38 % and 31 % of participants, respectively. Increasing oily fish intake was associated with a higher likelihood of FOS use (P < 0·001). Oily fish intake ≥ twice a week was the strongest predictor of high total n-3 PUFA (OR 6·7 (95 % CI 6·3, 7·1)) and DHA levels (6·6 (6·3, 7·1). FOS use was an independent predictor of high plasma n-3 PUFA levels (2·0 (2·0, 2·1)) with a similar OR to that associated with eating oily fish < once a week (1·9 (1·8, 2·0)). FOS use was associated with plasma n-3 PUFA levels that were similar to individuals in the next highest oily fish intake category. In conclusion, FOS use is more common in frequent fish consumers and modifies the relationship between oily fish intake and plasma n-3 PUFA levels in UKBB participants. If unaccounted for, FOS use may confound the relationship between dietary n-3 PUFA intake, blood levels of n-3 PUFAs and health outcomes.
Asunto(s)
Suplementos Dietéticos , Ácidos Grasos Omega-3 , Aceites de Pescado , Peces , Humanos , Aceites de Pescado/administración & dosificación , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-3/administración & dosificación , Reino Unido , Masculino , Femenino , Persona de Mediana Edad , Anciano , Dieta , Adulto , Bancos de Muestras Biológicas , Alimentos Marinos , Animales , Biobanco del Reino UnidoRESUMEN
BACKGROUND: A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences the expression of FADS1, which controls the synthesis of n-6 highly unsaturated fatty acid (HUFA) arachidonic acid (AA). The anti-inflammatory activity of the n-3 HUFA eicosapentaenoic acid (EPA) may be explained by competition with AA for proinflammatory lipid mediator synthesis. A precision medicine approach based on stratification by FADS Indel genotype could identify individuals, who benefit from greatest disease risk reduction by n-3 HUFAs. OBJECTIVES: We tested the hypothesis that the FADS insertion (I) allele predicts colorectal polyp risk reduction in a secondary analysis of the randomized, placebo-controlled, 2×2 factorial seAFOod polyp prevention trial of EPA 2000 mg daily and aspirin 300 mg daily for 12 mo (ISRCTN05926847). METHODS: Participant Indel genotype was determined by polymerase chain reaction (PCR) blind to trial outcomes. Colorectal polyp outcomes were included in negative binomial (polyp number) and logistic (polyp detection rate [PDR; percentage with one or more polyps]) regression models comparing each active intervention with its placebo. Presence of ≥1 Indel I allele and an interaction term (I allele × active intervention) were covariates. RESULTS: In 528 participants with colonoscopy and FADS Indel data, EPA use irrespective of Indel genotype, was not associated with reduced colorectal polyp number (incidence rate ratio [IRR]: 0.92; 95% confidence interval: 0.74, 1.16), mirroring original seAFOod trial analysis. However, the presence of ≥1 I allele identified EPA users with a significant reduction in colorectal polyp number (IRR: 0.50 [0.28, 0.90]), unlike aspirin, for which there was no interaction. Similar findings were obtained for the PDR. CONCLUSIONS: The FADS Indel I allele identified individuals, who displayed colorectal polyp prevention by EPA with a similar effect size to aspirin. Assessment of rs66698963 as a biomarker of therapeutic response to n-3 HUFAs in other populations and healthcare settings is warranted. The seAFOod polyp prevention trial and STOP-ADENOMA study were registered at International Standard Randomised Controlled Trial Number registry as ISRCTN05926847.
Asunto(s)
delta-5 Desaturasa de Ácido Graso , Ácido Eicosapentaenoico , Ácido Graso Desaturasas , Alimentos Marinos , Humanos , Femenino , Ácido Eicosapentaenoico/administración & dosificación , Masculino , Ácido Graso Desaturasas/genética , Persona de Mediana Edad , Anciano , Pólipos del Colon/genética , Mutación INDEL , Polimorfismo Genético , Neoplasias Colorrectales/prevención & control , Neoplasias Colorrectales/genética , Aspirina/administración & dosificación , Aspirina/uso terapéutico , GenotipoRESUMEN
INTRODUCTION: We examined the relationship between Apolipoprotein E (APOE) genotype and n-3 highly unsaturated fatty acid (HUFA) levels in participants of the seAFOod trial, who were undergoing colonoscopy surveillance after removal of colorectal polyps. METHODS: Baseline and on-treatment (eicosapentaenoic acid [EPA] 2 g daily or placebo for 6 months) levels of n-3 HUFAs, and plasma 18-hydroxyeicosapentaenoic acid (HEPE), were analysed according to APOE genotype (based on polymorphisms rs429358 and rs7412) in 584 participants. RESULTS: Before treatment, APOE2/2 individuals had lower levels, and APOE4/4 participants had higher levels, of n-3 HUFAs, including EPA, than APOE3/3 counterparts (P < 0.01 for the APOE2/2 versus APOE4/4 comparison). After EPA supplementation, n-3 HUFA levels were not significantly different when stratified by APOE genotype, although APOE4 carriers displayed lower plasma 18-HEPE levels than individuals without an APOE4 allele (P = 0.002). CONCLUSIONS: APOE genotype is associated with differential n-3 HUFA and 18-HEPE levels in individuals with multiple colorectal polyps.