Association of Plasma n-3 Polyunsaturated Fatty Acid Levels and the Prevalence of Frailty in Older Adults: A Cross-Sectional Analysis of UK Biobank.

BACKGROUND: Circulating levels of n-3 polyunsaturated fatty acids (PUFAs) have been associated with frailty among Koreans (a population with a high intake of fish), but whether this association exists in Western populations with low fish intake is unknown. The present study examined the hypothesis that the prevalence of frailty was inversely associated with plasma levels of n-3 PUFAs, with the intake of oily fish, and with fish oil supplementation in older adults in the United Kingdom. METHODS: UK Biobank including 79 330 adults aged ≥65 years with dietary data, and 18 802 participants with plasma fatty acid data were used. Frailty was defined using the Cardiovascular Health Study index, plasma levels of n-3 PUFAs were measured by nuclear magnetic resonance, and intake of oily fish and/or fish oil supplements was collected via food frequency questionnaire. RESULTS: Frailty prevalence was inversely associated with n-3 PUFA levels [odds ratios (OR) per SD: 0.86, 95% confidence interval (CI) 0.79-0.94; p < .001], with oily fish intake (never vs ≥2 servings per week; OR 0.59, 95% CI 0.52-0.68, p < .001), and with the use of fish oil supplements (OR 0.72; 95% CI 0.66-0.78; p < .001) after adjusting for confounding factors. All 3 exposures were also associated with each frailty criterion, particularly low physical activity and walking pace. CONCLUSIONS: Inverse associations between plasma n-3 PUFA levels and measures of frailty suggest that higher intakes of oily fish or the use of fish oil supplements may help prevent frailty in older adults in the United Kingdom.

Circulating Docosahexaenoic Acid and Risk of All-Cause and Cause-Specific Mortality.

OBJECTIVE: To assess the associations of docosahexaenoic acid (DHA), a marine omega-3 fatty acid, with long-term all-cause mortality, cardiovascular (CV) mortality, and cancer mortality. PATIENTS AND METHODS: We analyzed data from UK Biobank, which included 117,702 subjects with baseline plasma DHA levels and 12.7 years of follow-up between April 2007 and December 2021. Associations with risk for mortality endpoints were analyzed categorically by quintile of DHA plasma levels. RESULTS: Comparing the lowest to highest quintiles of circulating levels of DHA, there was 21% lower risk of all-cause mortality (HR, 0.79; 95% CI, 0.74 to 0.85; P<.0001). In a secondary analysis, we merged the UK Biobank findings with those from a recent FORCE (Fatty Acid and Outcome Research Consortium) meta-analysis that included 17 prospective cohort studies and 42,702 individuals examining DHA and mortality associations. The cumulative sample population included 160,404 individuals and 24,342 deaths during a median of 14 years of follow-up. After multivariable adjustment for relevant risk factors comparing the lowest to the highest quintiles of DHA, there was 17% lower risk of all-cause mortality (95% CI, 0.79 to 0.87; P<.0001), 21% lower risk for CV disease mortality (95% CI, 0.73 to 0.87; P<.001), 17% lower risk for cancer mortality (95% CI, 0.77 to 0.89; P<.0001), and 15% lower risk for all other mortality (95% CI, 0.79 to 0.91; P<.001). CONCLUSION: Higher DHA levels were associated with significant risk reductions in all-cause mortality, as well as reduced risks for deaths due to CV disease, cancer, and all other causes. The findings strengthen the hypothesis that DHA, a marine-sourced omega-3, may support CV health and lifespan.

Effects of niacin and omega-3 fatty acids on HDL-apolipoprotein A-I exchange in subjects with metabolic syndrome.

HDL-apolipoprotein A-I exchange (HAE) measures a functional property associated with HDL's ability to mediate reverse cholesterol transport. HAE has been used to examine HDL function in case-control studies but not in studies of therapeutics that alter HDL particle composition. This study investigates whether niacin and omega-3 fatty acids induce measurable changes in HAE using a cohort of fifty-six subjects with metabolic syndrome (MetS) who were previously recruited to a double-blind trial where they were randomized to 16 weeks of treatment with dual placebo, extended-release niacin (ERN, 2g/day), prescription omega-3 ethyl esters (P-OM3, 4g/day), or the combination. HAE was assessed at the beginning and end of the study. Compared to placebo, ERN and P-OM3 alone significantly increased HAE by 15.1% [8.2, 22.0] (P<0.0001) and 11.1% [4.5, 17.7] (P<0.0005), respectively, while in combination they increased HAE by 10.0% [2.5, 15.8] (P = 0.005). When HAE was evaluated per unit mass of apoA-I ERN increased apoA-I specific exchange activity by 20% (2, 41 CI, P = 0.02) and P-OM3 by 28% (9.6, 48 CI, P<0.0006). However the combination had no statistically significant effect, 10% (-9, 31 CI, P = 0.39). With regard to P-OM3 therapy in particular, the HAE assay detected an increase in this property in the absence of a concomitant rise in HDL-C and apoA-I levels, suggesting that the assay can detect functional changes in HDL that occur in the absence of traditional biomarkers.

Effect of six month's treatment with omega-3 acid ethyl esters on long-term outcomes after acute myocardial infarction: The OMEGA-REMODEL randomized clinical trial.

BACKGROUND: Omega-3 polyunsaturated fatty acids (O3-FA) have been shown to reduce inflammation and adverse cardiac remodeling after acute myocardial infarction (AMI). However, the impact of O3-FA on long-term clinical outcomes remains uncertain. AIMS: To investigate the impact of O3-FA on adverse cardiac events in long-term follow up post AMI in a pilot-study. METHODS: Consecutive patients with AMI were randomized 1:1 to receive 6 months of O3-FA (4 g/daily) or placebo in the prospective, multicenter OMEGA-REMODEL trial. Primary endpoint was a composite of major adverse cardiovascular events (MACE) encompassing all-cause death, heart failure hospitalizations, recurrent acute coronary syndrome, and late coronary artery bypass graft (CABG). RESULTS: A total of 358 patients (62.8% male; 48.1 ± 16.1 years) were followed for a median of 6.6 (IQR: 5.0-9.1) years. Among those receiving O3-FA (n = 180), MACE occurred in 65 (36.1%) compared to 62 (34.8%) of 178 assigned to placebo. By intention-to-treat analysis, O3-FA treatment assignment did not reduce MACE (HR = 1.014; 95%CI = 0.716-1.436; p = 0.938), or its individual components. However, patients with a positive response to O3-FA treatment (n = 43), defined as an increase in the red blood cell omega-3 index (O3I) ≥5% after 6 months of treatment, had lower annualized MACE rates compared to those without (2.9% (95%CI = 1.2-5.1) vs 7.1% (95%CI = 5.7-8.9); p = 0.001). This treatment benefit persisted after adjustment for baseline characteristics (HRadjusted = 0.460; 95%CI = 0.218-0.970; p = 0.041). CONCLUSION: In long-term follow-up of the OMEGA-REMODEL randomized trial, O3-FA did not reduce MACE after AMI by intention to treat principle, however, patients who achieved a ≥ 5% increase of O3I subsequent to treatment had favorable outcomes.

Omega-3 fatty acid supply in pregnancy for risk reduction of preterm and early preterm birth.

This clinical practice guideline on the supply of the omega-3 docosahexaenoic acid and eicosapentaenoic acid in pregnant women for risk reduction of preterm birth and early preterm birth was developed with support from several medical-scientific organizations, and is based on a review of the available strong evidence from randomized clinical trials and a formal consensus process. We concluded the following. Women of childbearing age should obtain a supply of at least 250 mg/d of docosahexaenoic+eicosapentaenoic acid from diet or supplements, and in pregnancy an additional intake of ≥100 to 200 mg/d of docosahexaenoic acid. Pregnant women with a low docosahexaenoic acid intake and/or low docosahexaenoic acid blood levels have an increased risk of preterm birth and early preterm birth. Thus, they should receive a supply of approximately 600 to 1000 mg/d of docosahexaenoic+eicosapentaenoic acid, or docosahexaenoic acid alone, given that this dosage showed significant reduction of preterm birth and early preterm birth in randomized controlled trials. This additional supply should preferably begin in the second trimester of pregnancy (not later than approximately 20 weeks' gestation) and continue until approximately 37 weeks' gestation or until childbirth if before 37 weeks' gestation. Identification of women with inadequate omega-3 supply is achievable by a set of standardized questions on intake. Docosahexaenoic acid measurement from blood is another option to identify women with low status, but further standardization of laboratory methods and appropriate cutoff values is needed. Information on how to achieve an appropriate intake of docosahexaenoic acid or docosahexaenoic+eicosapentaenoic acid for women of childbearing age and pregnant women should be provided to women and their partners.

Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies.

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium. METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction. RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions. CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Plasma Omega-3 Fatty Acids and Risk for Incident Dementia in the UK Biobank Study: A Closer Look.

Dietary omega-3 fatty acids are promising nutrients in dementia. Several prospective cohort studies have examined the relationships between circulating omega-3 (an objective biomarker of dietary intake) and incident dementia, the largest to date being a report from the UK Biobank (n = 102,722). Given the recent release of new metabolomics data from baseline samples from the UK Biobank, we re-examined the association in a much larger sample (n = 267,312) and also focused on associations with total omega-3, docosahexaenoic acid (DHA), and non-DHA omega-3. Using Cox regression models, we observed that the total omega-3 status was inversely related to the risk of Alzheimer's (Q5 vs. Q1, hazard ratio [95% confidence interval] = 0.87 [0.76; 1.00]) and all-cause dementia (Q5 vs. Q1, 0.79 [0.72; 0.87]). The strongest associations were observed for total omega-3 (and non-DHA omega-3) and all-cause dementia. In prespecified strata, we found stronger associations in men, and in those aged ≥60 years at baseline (vs. those aged 50-59). Thus, in the largest study to date on this topic, we confirmed the favorable relationships between DHA and risk for dementia, and we also found evidence that non-DHA omega-3 may be beneficial. Finally, we have better defined the populations most likely to benefit from omega-3-based interventions.

A Genome-Wide Interaction Study of Erythrocyte ω-3 Polyunsaturated Fatty Acid Species and Memory in the Framingham Heart Study Offspring Cohort.

BACKGROUND: Cognitive decline, and more specifically Alzheimer's disease, continues to increase in prevalence globally, with few, if any, adequate preventative approaches. Several tests of cognition are utilized in the diagnosis of cognitive decline that assess executive function, short- and long-term memory, cognitive flexibility, and speech and motor control. Recent studies have separately investigated the genetic component of both cognitive health, using these measures, and circulating fatty acids. OBJECTIVES: We aimed to examine the potential moderating effect of main species of ω-3 polyunsaturated fatty acids (PUFAs) on an individual's genetically conferred risk of cognitive decline. METHODS: The Offspring cohort from the Framingham Heart Study was cross-sectionally analyzed in this genome-wide interaction study (GWIS). Our sample included all individuals with red blood cell ω-3 PUFA, genetic, cognitive testing (via Trail Making Tests [TMTs]), and covariate data (N = 1620). We used linear mixed effects models to predict each of the 3 cognitive measures (TMT A, TMT B, and TMT D) by each ω-3 PUFA, single nucleotide polymorphism (SNP) (0, 1, or 2 minor alleles), ω-3 PUFA by SNP interaction term, and adjusting for sex, age, education, APOE ε4 genotype status, and kinship (relatedness). RESULTS: Our analysis identified 31 unique SNPs from 24 genes reaching an exploratory significance threshold of 1×10-5. Fourteen of the 24 genes have been previously associated with the brain/cognition, and 5 genes have been previously associated with circulating lipids. Importantly, 8 of the genes we identified, DAB1, SORCS2, SERINC5, OSBPL3, CPA6, DLG2, MUC19, and RGMA, have been associated with both cognition and circulating lipids. We identified 22 unique SNPs for which individuals with the minor alleles benefit substantially from increased ω-3 fatty acid concentrations and 9 unique SNPs for which the common homozygote benefits. CONCLUSIONS: In this GWIS of ω-3 PUFA species on cognitive outcomes, we identified 8 unique genes with plausible biology suggesting individuals with specific polymorphisms may have greater potential to benefit from increased ω-3 PUFA intake. Additional replication in prospective settings with more diverse samples is needed.

n-6 fatty acid biomarkers and incident atrial fibrillation: an individual participant-level pooled analysis of 11 international prospective studies.

BACKGROUND: The presence of atrial fibrillation (AF) is associated with an over 2-fold increased risk of stroke, heart failure, and cardiovascular mortality. Long chain n-6 PUFAs have been suggested to have a variety of beneficial biologic effects that may reduce AF development; however, prior studies evaluating this relationship are limited. OBJECTIVES: We prospectively evaluated the association between circulating levels of linoleic acid (LA) and arachidonic acid (AA) with incident AF. METHODS: We used participant-level data from a global consortium of 11 prospective cohort studies with measurements of LA and AA in adults (aged ≥18 y). Participating studies conducted de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcomes, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. RESULTS: Among 41,335 participants, 6173 incident cases of AF were ascertained, with median follow-up time of 14 y. In multivariable analysis, per interquintile range (difference between the 10th and 90th percentiles for each fatty acid), circulating n-6 levels were not associated with incident AF. For LA, the hazard ratio per interquintile range was 0.96 (95% confidence interval [CI]: 0.89, 1.04), and for AA, 1.02 (95% CI: 0.94, 1.10), with little evidence of heterogeneity between cohorts. Associations were similarly nonsignificant across subgroups of age, race, and biomarker fraction. CONCLUSIONS: Biomarkers of n-6 fatty acids including LA and AA are not associated with incident AF. These findings suggest that overall effects of n-6 PUFAs on influencing AF development are neutral.

Correction: Harris et al. Derivation of the Omega-3 Index from EPA and DHA Analysis of Dried Blood Spots from Dogs and Cats. Vet. Sci. 2023, 10, 13.

In the original publication [...].

Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation.

BACKGROUND: The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial. OBJECTIVES: This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF. METHODS: We used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes. Each participating study conducted a de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. RESULTS: Among 54,799 participants from 17 cohorts, 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively. CONCLUSIONS: In vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.

Genome-wide association study of Red Blood Cell fatty acids in the Women's Health Initiative Memory Study.

Despite their widespread associations with a wide variety of disease phenotypes, the genetics of red blood cell fatty acids remains understudied. We present one of the first genome-wide association studies of red blood cell fatty acid levels, using the Women's Health Initiative Memory study - a prospective cohort of N = 7,479 women aged 65-79. Approximately 9 million SNPs were measured directly or imputed and, in separate linear models adjusted for age and genetic principal components of ethnicity, SNPs were used to predict 28 different fatty acids. SNPs were considered genome-wide significant using a standard genome-wide significance level of p < 1 × 10-8. Twelve separate loci were identified, seven of which replicated results of a prior RBC-FA GWAS. Of the five novel loci, two have functional annotations directly related to fatty acids (ELOVL6 and ACSL6). While overall explained variation is low, the twelve loci identified provide strong evidence of direct relationships between these genes and fatty acid levels. Further studies are needed to establish and confirm the biological mechanisms by which these genes may directly contribute to fatty acid levels.

Adipose tissue n-3/n-6 fatty acids ratios versus n-3 fatty acids fractions as predictors of myocardial infarction.

BACKGROUND: Tissue levels of n-3 polyunsaturated fatty acids (PUFAs) have been inversely related with risk of myocardial infarction (MI). Whether ratios of n-3 to n-6 PUFAs, reflecting both dietary intake of n-3 PUFAs and competing n-6 PUFAs, are better predictors of future MI than n-3 PUFA fractions is unclear. We aimed at investigating whether such ratios in adipose tissue better predict MI than n-3 PUFA fractions. METHODS: Subcutaneous adipose tissue biopsies were obtained in a random sample (n = 3,500) of the Diet, Cancer and Health cohort (n = 57,053). Adipose tissue content of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), arachidonic acid (AA) and linoleic acid was determined using gas chromatography. Fractions of selected n-3 PUFAs and n-3/n-6 PUFA ratios were correlated to the 15-year occurrence of MI in a case-cohort design. RESULTS: A total of 2,406 participants experienced an MI during follow-up. Adipose tissue total marine n-3 PUFAs, EPA+DHA, EPA, EPA/AA, DHA/AA and (EPA + DPA + DHA)/AA were all inversely associated with risk of incident MI. Evaluating the predictive power (Harrel's C-index) of the selected metrics, fractions of marine n-3 PUFAs and ratios of EPA/AA, DHA/AA, (EPA + DHA)/AA and (EPA + DPA + DHA)/AA all refined risk prediction over age and sex alone. At multivariable analyses, however, the above ratios were the only metrics providing additional risk prediction. Differences in ratios were related to differences in food intake. CONCLUSIONS: Both adipose tissue n-3 PUFAs fractions and ratios of n-3 PUFAs/AA were associated with a lower occurrence of MI, but ratios provided superior risk prediction. Dietary strategies affecting n-3/n-6 PUFA ratios should be further investigated for prediction of MI with dietary interventions at the population level and in intervention studies.

Association between blood N-3 fatty acid levels and the risk of coronavirus disease 2019 in the UK Biobank.

BACKGROUND: The role of nutritional status and the risk of contracting and/or experiencing adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are unclear. Preliminary studies suggest that higher n-3 PUFA intakes are protective. OBJECTIVES: This study aimed to compare the risk of 3 coronavirus disease 2019 (COVID-19) outcomes (testing positive for SARS-CoV-2, hospitalization, and death) as a function of the baseline plasma DHA levels. METHODS: The DHA levels (% of total fatty acids [FAs]) were measured by nuclear magnetic resonance. The 3 outcomes and relevant covariates were available for 110,584 subjects (hospitalization and death) and for 26,595 ever-tested subjects (positive for SARS-CoV-2) in the UK Biobank prospective cohort study. Outcome data between 1 January, 2020, and 23 March, 2021, were included. The Omega-3 Index (O3I) (RBC EPA + DHA%) values across DHA% quintiles were estimated. The multivariable Cox proportional hazards models were constructed, and linear (per 1 SD) relations with the risk of each outcome were computed as HRs. RESULTS: In the fully adjusted models, comparing the fifth to the first DHA% quintiles, the HRs (95% confidence intervals) for testing positive, being hospitalized, and dying with COVID-19 were 0.79 (0.71, 0.89, P < 0.001), 0.74 (0.58, 0.94, P < 0.05), and 1.04 (0.69-1.57, not significant), respectively. On a per 1-SD increase in DHA% basis, the HRs for testing positive, hospitalization, and death, were 0.92 (0.89, 0.96, P < 0.001), 0.89 (0.83, 0.97, P < 0.01), and 0.95 (0.83, 1.09), respectively. The estimated O3I values across DHA quintiles ranged from 3.5% (quintile 1) to 8% (quintile 5). CONCLUSIONS: These findings suggest that nutritional strategies to increase the circulating n-3 PUFA levels, such as increased consumption of oily fish and/or use of n-3 FA supplements, may reduce the risk of adverse COVID-19 outcomes.

Lower omega-3 status associated with higher erythrocyte distribution width and neutrophil-lymphocyte ratio in UK Biobank cohort.

High red blood distribution width (RDW) is associated with decreased red blood cell deformability, and high neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and innate-adaptive immune system imbalance. Both RDW and NLR are predictors of chronic disease risk and mortality. Omega-3 index (O3I) values have previously been shown to be inversely associated with RDW and NLR levels. Our objective was to determine if total plasma long chain omega-3 fatty acids (Omega3%) measured in the UK Biobank cohort were associated with RDW and NLR values. RDW- and NLR- relationships with Omega3% were characterized in 109,191 adults (58.4% female). RDW- and NLR-Omega3% relationships were inversely associated with Omega3% (both p < 0.0001). These cross-sectional associations confirm previous findings that increasing RDW and NLR values are associated with low O3I. The hypothesis that RDW and/or NLR values can be reduced in individuals with less-than optimal long chain omega 3 values need to be tested in randomized controlled intervention trials using EPA and/or DHA.

Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts.

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD). DESIGN: Pooled analysis. DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020. STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate. DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis. MAIN OUTCOME MEASURES: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2 and <75% of baseline rate. RESULTS: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I2=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I2=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I2=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 v <60 years), estimated glomerular filtration rate (60-89 v ≥90 mL/min/1.73 m2), hypertension, diabetes, and coronary heart disease at baseline. CONCLUSIONS: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.

Estimation and predictors of the Omega-3 Index in the UK Biobank.

Information on the Omega-3 Index (O3I) in the United Kingdom (UK) is scarce. The UK-Biobank (UKBB) contains data on total plasma n3-PUFA% and DHA% measured by NMR. The aim of our study was to create an equation to estimate the O3I (eO3I) from these data. We first performed an inter-laboratory experiment with 250 random blood samples in which the O3I was measured in erythrocytes by GC, and total n3 % and DHA% were measured in plasma by NMR. The best predictor of eO3I included both DHA% and a derived metric, the total n3 %-DHA%. Together these explained 65 % of the variability (r = 0·832, P < 0·0001). We then estimated the O3I in 117 108 UKBB subjects and correlated it with demographic and lifestyle variables in multivariable-adjusted models. The mean eO3I was 5·58 % (sd 2·35 %) in this UKBB cohort. Several predictors were significantly correlated with eO3I (all P < 0·0001). In general order of impact and with directionality (-, inverse and +, direct): oily-fish consumption (+), fish oil supplement use (+), female sex (+), older age (+), alcohol use (+), smoking (-), higher waist circumference and BMI (-), lower socioeconomic status and less education (-). Only 20·5 % of eO3I variability could be explained by predictors investigated, and oily fish consumption accounted for 7·0 % of that. With the availability of the eO3I in the UKBB cohort, we will be in a position to link risk for a variety of diseases with this commonly used and well-documented marker of n3-PUFA biostatus.

Association between Omega-3 Index and Hyperglycemia Depending on Body Mass Index among Adults in the United States.

There is inconsistency regarding the association between long-chain n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA; 20:5n3) and docosahexaenoic acid (DHA; 22:6n3) and the risk of type 2 diabetes. The present study aimed to investigate the association between the Omega-3 Index (erythrocyte EPA + DHA) and glycemic status as a function of body mass index (BMI). Cross-sectional data from routine clinical laboratory testing with a total of 100,572 people aged over 18 years and BMI ≥ 18.5 kg/m2 were included. Of the patients, 10% were hyperglycemic (fasting plasma glucose levels ≥ 126 mg/dL) and 24.7% were of normal weight, 35.0% were overweight, and 40.3% were obese. Odds ratios (ORs) of being hyperglycemic were inversely associated with the Omega-3 Index, but weakened as BMI increased. Thus, ORs (95% CI) comparing quintile 5 with quintile 1 were 0.54 (0.44-0.66) in the normal weight group, 0.70 (0.61-0.79) in the overweight group, and 0.74 (0.67-0.81) in the obese group. Similar patterns were seen for EPA and DHA separately. The present study suggested that a low Omega-3 Index is associated with a greater risk of disordered glucose metabolism and this is independent of BMI.