Objective.\p=m-\To assess whether the dietary intake of long-chain n-3 polyunsaturated fatty acids from seafood, assessed both directly and indirectly through a biomarker, is associated with a reduced risk of primary cardiac arrest.Design.\p=m-\Population-based case-control study.Setting.\p=m-\Seattle and suburban King County, Washington. Participants\p=m-\A total of 334 case patients with primary cardiac arrest, aged 25 to 74 years, attended by paramedics during 1988 to 1994 and 493 population-based control cases and controls, matched for age and sex, randomly identified from the community. All cases and controls were free of prior clinical heart disease, major comorbidity, and use of fish oil supplements.Measures of Exposure.\p=m-\Spouses of case patients and control subjects were interviewed to quantify dietary n-3 polyunsaturated fatty acid intake from seafood during the prior month and other clinical characteristics. Blood specimens from 82 cases (collected in the field) and 108 controls were analyzed to determine red blood cell membrane fatty acid composition, a biomarker of dietary n-3 polyunsaturated fatty acid intake.Results.\p=m-\Compared with no dietary intake of eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3), an intake of 5.5 g of n-3 fatty acids per month (the mean of the third quartile and the equivalent of one fatty fish meal per week) was associated with a 50% reduction in the risk of primary cardiac arrest (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4 to 0.8), after adjustment for potential confounding factors. Compared with a red blood cell membrane n-3 polyunsaturated fatty acid level of 3.3% of total fatty acids (the mean of the lowest quartile), a red blood cell n-3 polyunsaturated fatty acid level of 5.0% of total fatty acids (the mean of the third quartile) was associated with a 70% reduction in the risk of primary cardiac arrest (OR, 0.3; 95% CI, 0.2 to 0.6).Conclusion.\p=m-\Dietary intake of n-3 polyunsaturated fatty acids from seafood is associated with a reduced risk of primary cardiac arrest.

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3×10−64) and lower levels of eicosapentaenoic acid (EPA, p = 5×10−58) and docosapentaenoic acid (DPA, p = 4×10−154). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2×10−12) and DPA (p = 1×10−43) and lower docosahexaenoic acid (DHA, p = 1×10−15). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1×10−8). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.

Background-Palmitoleic acid (cis-16:1n-7), produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative.

Vitamin and mineral supplements are among the most commonly used drugs in the United States, despite limited evidence on their benefits or risks. This paper describes the design, implementation, and participant characteristics of the VITamins And Lifestyle (VITAL) Study, a cohort study of the associations of supplement use with cancer risk. A total of 77,738 men and women in western Washington State, aged 50-76 years, entered the study in 2000-2002 by completing a detailed questionnaire on supplement use, diet, and other cancer risk factors, and 70% provided DNA through self-collected buccal cell specimens. Supplement users were targeted in recruitment: 66% used multivitamins, 46% used individual vitamin C, 47% used individual vitamin E, and 46% used calcium, typically for 5-8 of the past 10 years. Analyses to identify confounding factors, the main study limitation, showed that regular nonsteroidal anti-inflammatory drug use, intake of fruits and vegetables, and recreational physical activity were strongly associated with supplement use (p < 0.001). The authors describe a follow-up system in which cancers, deaths, and changes of residence are tracked efficiently, primarily through linkage to public databases. These methods may be useful to other researchers implementing a large cohort study or designing a passive follow-up system.

Higher combined dietary intake of DHA and EPA, and possibly alpha-linolenic acid, may lower the risk of fatal ischemic heart disease in older adults. The association of n-3 polyunsaturated fatty acids with fatal ischemic heart disease, but not with nonfatal myocardial infarction, is consistent with possible antiarrhythmic effects of these fatty acids.

Background Omega-6 (n6) polyunsaturated fatty acids (PUFAs) and their metabolites are involved in cell signaling, inflammation, clot formation, and other crucial biological processes. Genetic components, such as variants of fatty acid desaturase (FADS) genes, determine the composition of n6 PUFAs. Methods and Results To elucidate undiscovered biologic pathways that may influence n6 PUFA composition, we conducted genome-wide association studies and meta-analyses of associations of common genetic variants with five plasma n6 PUFAs in 8,631 Caucasian adults (55% female) across five prospective studies. Plasma phospholipid or total plasma fatty acids were analyzed by similar gas chromatography techniques. The n6 fatty acids linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma-linoleic acid (DGLA), arachidonic acid (AA), and adrenic acid (AdrA) were expressed as % of total fatty acids. We performed linear regression with robust standard errors to test for SNP-fatty acid associations, with pooling using inverse-variance weighted meta-analysis. Novel regions were identified on chromosome 10 associated with LA (rs10740118, p-value = 8.1x10−9; near NRBF2); on chromosome 16 with LA, GLA, DGLA, and AA ( rs16966952, p-value = 1.2×10−15, 5.0×10−11, 7.6×10−65, and 2.4×10−10, respectively; NTAN1); and on chromosome 6 with AdrA following adjustment for AA (rs3134950, p-value = 2.1×10−10; AGPAT1). We confirmed previous findings of the FADS cluster on chromosome 11 with LA and AA, and further observed novel genome-wide significant association of this cluster with GLA, DGLA, and AdrA (p-value = 2.3×10−72, 2.6×10−151, and 6.3×10−140, respectively). Conclusions Our findings suggest that along with the FADS gene cluster, additional genes may influence n6 PUFA composition.

Background Long-chain n-3 polyunsaturated fatty acids (n3-PUFA), including eicosapentaenoic acid (EPA/20:5n-3), docosapentaenoic acid (DPA/22:5n-3), and docosahexaenoic acid (DHA/22:6n-3), experimentally reduce cardiovascular risk. Yet, effects on cause-specific and total mortality and potential dose-responses remain controversial. Most observational studies have assessed self-reported dietary intakes, rather than objective biomarkers; while most randomized trials have tested effects of adding supplements to background dietary intake and evaluated secondary prevention, limiting inference for dietary n3-PUFA or primary prevention. Objective We investigated associations of plasma phospholipid EPA, DPA, DHA, and total n-3 PUFA with total and cause-specific mortality among generally healthy older adults not taking fish oil supplements. Design Prospective cohort, 1992–2008. Setting Four U.S. communities. Participants 2,692 U.S. adults age 75±5 years, free of prevalent coronary heart disease (CHD), stroke, or heart failure. Measurements Phospholipid fatty acids and cardiovascular risk factors were measured in 1992 using standardized methods. Relationships with total and cause-specific mortality through 2008, and incident total (fatal+nonfatal) CHD and stroke, were assessed using Cox proportional-hazards. Results During 30,829 person-years, 1,625 deaths (including 570 cardiovascular deaths), 359 fatal and 371 nonfatal CHD events, and 130 fatal and 276 nonfatal strokes occurred. After multivariable-adjustment, n3-PUFA biomarkers associated with lower total mortality, with extreme-quintile hazard ratios (95% CI) of 0.83 for EPA (0.71–0.98), 0.77 for DPA (0.66–0.90), 0.80 for DHA (0.67–0.94), and 0.73 for total n3-PUFA (0.61–0.86) (P-trend≤0.008 each). Lower risk was largely attributable to fewer cardiovascular, rather than noncardiovascular, deaths, in particular fewer arrhythmic cardiac deaths (total n3-PUFA: hazard ratio=0.52, 95%CI=0.31–0.86; P-trend=0.008). Based on relations with total mortality, individuals in the highest quintile of phospholipid n3-PUFA, versus the lowest, experienced 2.22 greater years of life (95%CI=0.75–3.13) after age 65. Limitations Temporal changes in fatty acid levels and misclassification of death causes may cause underestimated associations; and unmeasured/imperfectly measured covariates, residual confounding. Conclusions Circulating individual and total n3-PUFA are associated with lower total mortality, especially CHD death, in older adults. Primary Funding Source National Institutes of Health.

Adiposity (energy imbalance), carbohydrate consumption, and alcohol use-even within typical ranges-are associated with higher circulating palmitoleate concentrations. Circulating palmitoleate is robustly associated with multiple metabolic risk factors but in mixed directions, perhaps related to divergent lifestyle determinants or endogenous sources (liver, adipose tissue) of fatty acid synthesis.