Polyunsaturated Fatty Acids Biomarkers Research Articles

The Associations of Prenatal Exposure to Fine Particulate Matter and Its Chemical Components with Allergic Rhinitis in Children and the Modification Effect of Polyunsaturated Fatty Acids: A Birth Cohort Study.

Polyunsaturated fatty acids (PUFAs) have been shown to protect against fine particulate matter in aerodynamic diameter ()-induced hazards. However, limited evidence is available for respiratory health, particularly in pregnant women and their offspring. We aimed to investigate the association of prenatal exposure to and its chemical components with allergic rhinitis (AR) in children and explore effect modification by maternal erythrocyte PUFAs. This prospective birth cohort study involved 657 mother-child pairs from Guangzhou, China. Prenatal exposure to residential mass and its components [black carbon (BC), organic matter (OM), sulfate (), nitrate (), and ammonium ()] were estimated by an established spatiotemporal model. Maternal erythrocyte PUFAs during pregnancy were measured using gas chromatography. The diagnosis of AR and report of AR symptoms in children were assessed up to 2 years of age. We used Cox regression with the quantile-based g-computation approach to assess the individual and joint effects of components and examine the modification effects of maternal PUFA levels. Approximately and 8.07% of children had AR and related symptoms, respectively. The average concentration of prenatal was . was positively associated with the risk of developing AR [hazard ratio ; 95% confidence interval (CI): 1.16, 2.96 per ] and its symptoms (; 95% CI: 1.22, 2.62 per ) after adjustment for confounders. Similar associations were observed between individual components and AR outcomes. Each quintile change in a mixture of components was associated with an adjusted HR of 3.73 (95% CI: 1.80, 7.73) and 2.69 (95% CI: 1.55, 4.67) for AR and AR symptoms, with BC accounting for the largest contribution. Higher levels of n-3 docosapentaenoic acid and lower levels of n-6 linoleic acid showed alleviating effects on AR symptoms risk associated with exposure to and its components. Prenatal exposure to and its chemical components, particularly BC, was associated with AR/symptoms in early childhood. We highlight that PUFA biomarkers could modify the adverse effects of on respiratory allergy. https://doi.org/10.1289/EHP13524.

Fatty Acid Intake and Polyunsaturated Fatty Acid Biomarkers and Risk of Total Knee or Hip Arthroplasty Among Older Women in the Women's Health Initiative.

The objective was to determine whether baseline fatty acid intake and erythrocyte omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can predict risk of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in older women. This was a prospective analysis of 34,990 women in the Women's Health Initiative. Dietary fatty acids were estimated from food frequency questionnaires. Imputed erythrocyte PUFAs were available in a subcohort of 3,428 women. Arthroplasty (THA and TKA), used as a surrogate of severe osteoarthritis, was identified via linked Medicare data. Cox proportional hazards models were constructed to estimate risk of arthroplasty. Risk of THA was associated with higher intake of arachidonic acid, (multivariable hazard ratio [HR] quartile 4 [Q4] vs Q1: 1.16; 95% confidence interval [CI] 1.01-1.34; P = 0.03) and higher intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; HR Q4 vs Q1: 1.20; 95% CI 1.05-1.39; P = 0.003). There was a linear trend (P = 0.04) for patients to have a higher risk of THA with higher erythrocyte EPA and DHA in body mass index-adjusted models; however, there was no significant difference in patients who had THAs by quartiles of erythrocyte EPA and DHA (P = 0.10). Dietary fatty acids and erythrocyte PUFAs were not significantly associated with risk of TKA. Higher baseline intakes of arachidonic acid and EPA and DHA were associated with a modestly higher risk of THA. No association was found between fatty acids and patients who had TKAs. Further research in populations with direct measures of osteoarthritis severity is needed to better understand the importance of PUFAs in modulating osteoarthritis and arthroplasty risk.

Omega-3 polyunsaturated fatty acid biomarkers and risk of type 2 diabetes, cardiovascular disease, cancer, and mortality

Considerable attention has focused on the role of omega-3 polyunsaturated fatty acids (PUFA) in the prevention of cardiometabolic diseases, which has led to dietary recommendations to increase omega-3 fatty acid intake. A meta-analysis was conducted to summarize evidence from prospective studies regarding associations between omega-3 PUFA biomarkers and risk of developing major chronic diseases. Four electronic databases were searched for articles from inception to March 1, 2022. Random-effects model was used to estimate the pooled relative risk (RR) and 95% confidence intervals (CIs) for the association of omega-3 PUFAs, including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), with risk of developing type 2 diabetes (T2D), cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, cancer, and mortality. The Grades of Recommendation, Assessment, Development and Evaluation assessment tool was used to rates the confidence in estimates. A total of 67 prospective studies comprised of 310,955 participants were identified. Individual omega-3 PUFAs showed divergent associations with the study outcomes of interest. A significant inverse association with T2D risk was observed across categories of ALA (relative risk [RR]: 0.89, 95% confidence interval [CI]: 0.82-0.96), EPA (RR: 0.85, 95% CI: 0.72-0.99) and DPA (RR: 0.84, 95% CI: 0.73-0.96) biomarkers. The marine-origin omega-3 fatty acids biomarkers but not ALA was significantly associated with lower risks of total CVD, CHD, and overall mortality, with RRs ranging from 0.70 for DHA-CHD association to 0.85 for EPA-CHD association. A lower risk of colorectal cancer was observed at higher levels of DPA (RR: 0.76, 95% CI: 0.59-0.98) and DHA (RR: 0.80; 95% CI: 0.65-0.99), whereas no association was noted for other outcomes. In addition, a dose-response relationship was observed between an increasing level of EPA, DPA, or DHA biomarker and lower risk of CVD. Higher concentrations of marine-derived omega-3 PUFA biomarkers were associated with a significantly reduced risk of total CVD, CHD, and total mortality. Levels of ALA were inversely associated with a lower risk of T2D but not CVD-related outcomes. These data support the dietary recommendations advocating the role of omega-3 PUFAs in maintaining an overall lower risk of developing cardiovascular disease and premature deaths.

Twelve Weeks of Additional Fish Intake Improves the Cognition of Cognitively Intact, Resource-Limited Elderly People: A Randomized Control Trial.

Dietary omega 3 polyunsaturated fatty acids (PUFA) may reduce the risk of dementia. Many studies have investigated PUFA supplementation in high-income countries, yet food-based randomized control trials using omega 3 PUFA rich fish in lower to middle income countries, are lacking. To determine the effect on cognition of adding either fish or non-fish foods for twelve weeks to an enhanced diet of cognitively intact, independently living, resource-limited elderly people. Randomized control trial (National Health Trial register: DOH-27-061-6026). Retirement center in urban South Africa. Fifty-seven (74% female, mean age: 72±7 years) elderly participants with cognitive function exceeding 22 on the Mini Mental State Examination were randomized into an intervention (n=31) and control (n=26) group. The usual diets of both groups were enhanced with context-appropriate foods to mimic elements of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. The intervention group additionally received canned pilchards and fish spread every week amounting to an additional (theoretical) intake of 2.2g omega 3 PUFA daily. The control group received canned meatballs and texturized soya every week. Cognition was measured twice before and once after the intervention phase using the Cognitive Abilities Screening Instrument (CASI). Adherence was assessed by a study-specific food frequency questionnaire and red blood cell (RBC) PUFA biomarkers. Data were analyzed using a non-parametric analysis of covariance (ANCOVA) with, and without, bootstrap imputation. Participants in the intervention group had a significantly higher post intervention (P=0.036) CASI score than the control group, when the model was fitted with imputation and controlled for baseline scores. Participants in the intervention group also had a significantly higher intake of calculated dietary omega 3 PUFA and higher levels of RBC eicosapentaenoic acid and docosapentaenoic acid content than the control group (P < 0.05). Twelve weeks of fish intake in the context of a modified MIND diet may improve the cognition of cognitively intact, resource-limited elderly people.

Assessment of polyunsaturated fatty acids: A self-report and biomarker assessment with a racially and ethnically diverse sample of women

Polyunsaturated fatty acids (PUFAs) play an important role in human health, influencing chronic disease and mortality. Food Frequency Questionnaires (FFQs) are widely used to assess self-reported diet, but they can be subject to a variety of errors. Accordingly, an accurate assessment of diet is crucial in nutrition research. This study examined the association between a widely-used self-report measure of PUFAs (Diet History Questionnaire-II: DHQ-II) with the proportion of PUFA in red blood cell (RBC) membranes, and examined whether this relationship was moderated by race/ethnicity. In a racially and ethnically diverse sample of 132 female participants (Mage = 21.97±3.98, range 18 to 42 years), bivariate correlations and linear regression analyses demonstrated associations between DHQ-II and proportion of nutrients in RBCs for omega-3 fatty acids EPA (r = 0.39, ß = 0.38, p < .01), DHA (r = 0.48, ß = 0.47, p < .01), and EPA+DHA (r = 0.51, β = 0.49, p < .01). No associations were found for omega-3 fatty acid ALA or omega-6 fatty acids LA or ARA. DHQ-II and RBC associations for EPA, DHA, and EPA+DHA were moderated by race/ethnicity, controlling for age. Self-report of EPA was most consistent with RBC proportions for Caucasian individuals, and less consistent for Black/African American individuals. Self-reports of DHA and EPA+DHA were most consistent with RBC proportions for Caucasian individuals, and less consistent for Black/African American individuals and Hispanic/Latina individuals, although still statistically significant. No associations were detected for Hispanic/Latina individuals (for EPA only), Asian/Pacific Islanders or individuals of mixed/other descent. The present study found that when compared to PUFA biomarkers, the DHQ-II did not assess PUFAs consistently across all racial/ethnic groups in this sample of women. Further research is needed to determine what factors contribute to weak or lacking correlations between reported fat intake and corresponding values in RBCs, including but not limited to recall errors, underestimations of fatty acids in food composition databases, insufficient DHQ-II assessment of fatty acids in general and from particular cultures, and genetic differences in fat metabolism.

Erythrocyte n-6 Polyunsaturated Fatty Acids, Gut Microbiota, and Incident Type 2 Diabetes: A Prospective Cohort Study.

OBJECTIVETo examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes and explore the potential role of gut microbiota in the association.RESEARCH DESIGN AND METHODSWe evaluated 2,731 participants without type 2 diabetes recruited between 2008 and 2013 in the Guangzhou Nutrition and Health Study (Guangzhou, China). Case subjects with type 2 diabetes were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset (n = 1,591), 16S rRNA profiling was conducted. Using multivariable-adjusted Poisson or linear regression, we examined associations of erythrocyte n-6 PUFA biomarkers with incident type 2 diabetes and diversity and composition of gut microbiota.RESULTSOver 6.2 years of follow-up, 276 case subjects with type 2 diabetes were identified (risk 0.10). Higher levels of erythrocyte γ-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher type 2 diabetes incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% CI 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both P < 0.05) during follow-up and significantly associated with microbiota β-diversity (P = 0.002). α-Diversity acted as a potential mediator in the association between GLA and type 2 diabetes (P < 0.05). Seven genera (Butyrivibrio, Blautia, Oscillospira, Odoribacter, S24-7 other, Rikenellaceae other, and Clostridiales other) were enriched in quartile 1 of GLA and in participants without type 2 diabetes.CONCLUSIONSRelative concentrations of erythrocyte GLA were positively associated with incident type 2 diabetes in a Chinese population and also with gut microbial profiles. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and type 2 diabetes etiology.

Erythrocyte n-6 Polyunsaturated Fatty Acids, Gut Microbiota and Incident Type 2 Diabetes: A Prospective Cohort Study

Abstract Objectives To examine the prospective association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes (T2D), and the potential role of gut microbiota. Methods 2731 non-T2D participants recruited between 2008–2013 in the Guangzhou Nutrition and Health Study were included in the present study. 276 incident T2D was ascertained after a median follow-up of 6.2 years, and 16S rRNA profiling was conducted using stool samples collected during follow-up. We examined the prospective association of erythrocyte n-6 PUFA biomarkers with incident T2D, and with diversity and composition of gut microbiota. Results Higher levels of erythrocyte γ-linolenic acid (GLA) were associated with higher T2D risk, with relative risk (quartile 4 versus 1) 1.72 (95% confidence intervals: 1.21, 2.44), adjusting for potential confounders. No association with T2D was found for erythrocyte linoleic acid or arachidonic acid. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both P &amp;lt; 0.05) during follow-up, and significantly associated with microbiota β-diversity (P = 0.002). Seven genera (Butyrivibrio, Blautia, Oscillospira, Odoribacter, S24–7 other, Rikenellaceae other, and Clostridiales other) were enriched in quartile 1 of GLA, and in participants without T2D. Conclusions The present study suggests that erythrocyte GLA biomarker is positively associated with incident T2D in a Chinese population. High GLA status is associated with unfavorable gut microbial profiles, which may contribute to the increased risk of T2D. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and T2D etiology. Funding Sources This study was funded by the National Natural Science Foundation of China, Westlake University and the 5010 Program for Clinical Researches of the Sun Yat-sen University.

Serum Polyunsaturated Fatty Acids in Middle Childhood and Body Mass Index Change Through Adolescence

Background: Polyunsaturated fatty acids (PUFA) status in childhood may be associated with adiposity development. Objective: To assess associations of serum PUFA biomarkers in childhood with change in body mass index (BMI)-for-age Z scores (BMIZ) through adolescence. Methods: We quantified serum PUFA at ages 5 and 10 years among 418 children from Santiago, Chile. BMI was measured at 5, 10, and 16 years. We compared BMIZ change through age 16 years between quartiles of PUFA at 5 and 10 years and PUFA change 5–10 years by fitting growth curves from mixed effects models. Results: At age 5 years, serum docosahexaenoic acid was inversely associated with BMIZ change from ages 5 to 16 years. At age 10 years, arachidonic acid (AA) was nonlinearly positively related to BMIZ change from ages 10 to 16 years. Change in AA and the Δ5-desaturase (D5D) activity index between 5 and 10 years were each positively associated with BMIZ change from ages 10 to 16 years. Change in eicosapentaenoic acid was inversely associated with change in BMIZ. Conclusions: Serum long-chain n-3 PUFA in middle childhood were associated with less BMI gain through adolescence, whereas AA and D5D activity was related to greater BMI gain.

Abstract 046: Longitudinal Associations of Omega-6 and Omega-3 Plasma Phospholipid Polyunsaturated Fatty Acids With Dementia in Older Adults: the Cardiovascular Health Study

Background: Polyunsaturated fatty acids (PUFA) are essential nutrients for normal brain function, constituting nearly 35% of brain lipids. Experimental studies suggest that omega-3 and omega-6 PUFA, present in plant foods and fish, may reduce risk of dementia. Most prior studies assessed self-reported estimates and used one baseline measure of objective PUFA biomarkers, which may lead to poor estimation of long-term risk. Aims: Investigate prospective associations of serial measures of plasma phospholipid omega-3 (ALA [18:3], EPA [20:5], DPA [22:5], DHA [22:6]) and omega-6 (LA [18:2], AA [20:4]) PUFA with risk of total dementia and dementia subtypes (Alzheimer’s Disease [AD] and vascular and mixed dementia [VaD]) in older adults in the Cardiovascular Health Study. Methods: Among 3,307 U.S. adults aged ≥65y and free of stroke, cognitive impairment or dementia at baseline, circulating levels were measured serially at baseline, 6 years and 13 years using standardized methods. Dementia was identified using neuropsychological tests or hospitalization records adjudicated by CHS Cognition Study investigators, and by ICD-9 codes from linked Medicare administrative data. Prospective associations were assessed by multivariate-adjusted Cox models incorporating time-varying fatty acid measures and covariates. Results: During 22,288 person-years of follow-up (1992-2015), 1,164 dementia cases were identified, with 530 AD and 256 VaD cases. After adjustment for demographic, lifestyle and dietary factors, higher circulating levels of AA were associated with lower risk of total dementia and AD (see Table). There were no statistically significant associations between circulating omega-3 PUFA or LA and incident dementia. Conclusion: In older adults, higher circulating AA was inversely associated with risk of total dementia and AD, but not other dementia subtypes. These findings highlight the need to identify mechanisms influencing circulating AA levels that could be effective for the prevention of dementia later in life.

Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies

The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m2, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60-0·72, p<0·0001; I2=53·9%, pheterogeneity=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88-1·05; p=0·38; I2=63·0%, pheterogeneity<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all pheterogeneity≥0·13). Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful. Funders are shown in the appendix.

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD. A global consortium of 19 studies identified by November 2014. Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes. Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the Multi-Ethnic Study of Atherosclerosis.

BackgroundDietary guidelines support intake of polyunsaturated fatty acids (PUFAs) in fish and vegetable oils. However, some controversy remains about benefits of PUFAs, and most prior studies have relied on self‐reported dietary assessment in relatively homogeneous populations.Methods and ResultsIn a multiethnic cohort of 2837 US adults (whites, Hispanics, African Americans, Chinese Americans), plasma phospholipid PUFAs were measured at baseline (2000–2002) using gas chromatography and dietary PUFAs estimated using a food frequency questionnaire. Incident cardiovascular disease (CVD) events (including coronary heart disease and stroke; n=189) were prospectively identified through 2010 during 19 778 person‐years of follow‐up. In multivariable‐adjusted Cox models, circulating n‐3 eicosapentaenoic acid and docosahexaenoic acid were inversely associated with incident CVD, with extreme‐quartile hazard ratios (95% CIs) of 0.49 for eicosapentaenoic acid (0.30 to 0.79; Ptrend=0.01) and 0.39 for docosahexaenoic acid (0.22 to 0.67; Ptrend<0.001). n‐3 Docosapentaenoic acid (DPA) was inversely associated with CVD in whites and Chinese, but not in other race/ethnicities (P‐interaction=0.01). No significant associations with CVD were observed for circulating n‐3 alpha‐linolenic acid or n‐6 PUFA (linoleic acid, arachidonic acid). Associations with CVD of self‐reported dietary PUFA were consistent with those of the PUFA biomarkers. All associations were similar across racial‐ethnic groups, except those of docosapentaenoic acid.ConclusionsBoth dietary and circulating eicosapentaenoic acid and docosahexaenoic acid, but not alpha‐linolenic acid or n‐6 PUFA, were inversely associated with CVD incidence. These findings suggest that increased consumption of n‐3 PUFA from seafood may prevent CVD development in a multiethnic population.