Plasma Polyunsaturated Fatty Acid Concentrations Research Articles

Evaluation of inflammatory hyperreflective foci and plasma EPA as diagnostic and predictive markers for age-related macular degeneration.

To detect the plasma polyunsaturated fatty acids (PUFAs) concentrations in age-related macular degeneration (AMD) patients and healthy controls. Additionally, advanced studies were conducted to investigate the relationship between PUFAs concentrations and ophthalmological characteristics, including hyperreflective foci (HRF), visual acuity, and anti-vascular endothelial growth factor (anti-VEGF) response in patients with AMD. This prospective, single-site study recruited a total of 315 participants, consisting of 105 individuals with dry AMD (early-stage AMD group), 105 individuals with neovascular AMD (late-stage AMD group), and 105 elderly individuals without any fundus diseases (healthy controls). The levels of omega-3 and omega-6 PUFAs in plasma were detected using gas chromatography. Retinal thickness, choroidal thickness, and macular volume were quantified using optical coherence tomography angiography (OCTA) scan with a 6 × 6 mm macular area, and the amounts of HRF were analyzed with OCTA scanning data. Compared to the control group, AMD patients exhibited significantly lower plasma concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha linolenic acid. HRF were observed in various retinal layers of AMD patients, particularly those with late-stage AMD. The correlation coefficient matrix and multiple linear regression models demonstrated that HRF played a crucial role in best corrected visual acuity for both early (p < 0.001) and late-stage AMD patients (p = 0.006), while EPA had an inverse effect on the logarithm of the minimum angle of resolution (logMAR) value in patients with early-stage AMD (p < 0.001). As compared to patients with good responses to anti-VEGF therapy, those with poor responses had significantly lower baseline logMAR (p < 0.001), central retina thickness (p = 0.002), macular volume (p = 0.027), HRF (p = 0.024), and plasma EPA (p < 0.001). This study used a ROC curve analysis to identify the combination of HRF and EPA as a potential biomarker for predicting the response to anti-VEGF treatment in late-stage AMD patients, with an area under the curve (AUC) value of 0.775. Reduced plasma EPA was detected in AMD cases and the lower EPA concentration was related to poorer visual acuity. Additionally, the quantity of HRF combined with concentration of plasma EPA may serve as the prognostic indicator for predicting the effect of anti-VEGF treatment in late-stage AMD patients.

Omega-3 Polyunsaturated Fatty Acid Levels in Maternal and Cord Plasma Are Associated with Maternal Socioeconomic Status.

Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) play a crucial role in fetal growth and neurodevelopment, while omega-6 (n-6) PUFAs have been associated with adverse pregnancy outcomes. Previous studies have demonstrated that socioeconomic status (SES) influences dietary intake of n-3 and n-6 PUFAs, but few studies have evaluated the association between maternal and cord plasma biomarkers of PUFAs and socioeconomic markers. An IRB-approved study enrolled mother-infant pairs (n = 55) at the time of delivery. Maternal and cord plasma PUFA concentrations were analyzed using gas chromatography. Markers of SES were obtained from validated surveys and maternal medical records. Mann-Whitney U tests and linear regression models were utilized for statistical analysis. Maternal eicosapentaenoic acid (EPA) (p = 0.02), cord EPA (p = 0.04), and total cord n-3 PUFA concentrations (p = 0.04) were significantly higher in college-educated mothers vs. mothers with less than a college education after adjustment for relevant confounders. Insurance type and household income were not significantly associated with n-3 or n-6 PUFA plasma concentrations after adjustment. Our findings suggest that mothers with lower educational status may be at risk of lower plasma concentrations of n-3 PUFAs at delivery, which could confer increased susceptibility to adverse pregnancy and birth outcomes.

Plasma polyunsaturated fatty acid concentrations and sleep apnea risk: A two-sample Mendelian randomization study.

BackgroundPrevious observational studies have found that lower levels of circulating polyunsaturated fatty acids (PUFAs) were associated with a higher risk of sleep apnea (SA). However, the causality of the association remains unclear.Materials and methodsWe used the two-sample Mendelian randomization (MR) study to assess the causal association of omega-3 and omega-6 fatty acids with SA. Single-nucleotide polymorphisms (SNPs) predicting the plasma level of PUFAs at the suggestive genome-wide significance level (p < 5 × 10–6) were selected as instrumental variables (IVs) from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) (n = ∼8,000) Consortium. For outcomes, the summary-level statistics of SA were obtained from the latest genome-wide association study (GWAS), which combined five cohorts with a total number of 25,008 SA cases and 172,050 snoring cases (total = 523,366).ResultsWe found no association of α-linolenic acid (ALA) [odds ratio (OR) = 1.09 per% changed, 95% confidence interval (CI) 0.67–1.78], eicosapentaenoic acid (EPA) (OR = 0.94, 95% CI 0.88–1.01), docosapentaenoic acid (DPA) (OR = 0.95, 95% CI 0.88–1.02), and docosahexaenoic acid (DHA) (OR = 0.99, 95% CI 0.96–1.02) with the risk of SA using inverse-variance weighted (IVW) method. Moreover, for omega-6 PUFAs, no association between linoleic acid (LA) (OR = 0.98, 95% CI 0.96–1.01), arachidonic acid (AA) (1.00, 95% CI 0.99–1.01), and adrenic acid (AdrA) (0.93, 95% CI 0.71–1.21) with the risk of SA was found. Similarly, no associations of PUFAs with SA were found in single-locus MR analysis.ConclusionIn the current study, we first found that there is no genetic evidence to support the causal role of omega-3 and omega-6 PUFAs in the risk of SA. From a public health perspective, our findings refute the notion that consumption of foods rich in PUFAs or the use of PUFAs supplementation can reduce the risk of SA.

Associations of Vitamin B6 Intake and Plasma Pyridoxal 5'-Phosphate with Plasma Polyunsaturated Fatty Acids in US Older Adults: Findings from NHANES 2003-2004.

Previous evidence suggests a potential dual impact of aging and vitamin B6 (B6) deficiency on polyunsaturated fatty acid (PUFA) metabolism; gender may influence PUFA biosynthesis. Perturbation of PUFA compositions during B6 deficiency could be linked to age-related health outcomes. However, little is known about the interrelationships between vitamin B6, PUFA, and gender in the older population. Therefore, we investigated whether gender-specific associations of B6 intake and plasma pyridoxal 5’-phosphate (PLP) concentration, respectively, with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, and (EPA + DHA)/AA) existed in older adults. We further examined the relationships of adequate B6 status (PLP ≥ 20 nmol/L) with high (above median) plasma PUFA relative to deficient B6 status. This cross-sectional study analyzed 461 participants aged ≥60 years from NHANES 2003–2004. Nutrient intakes were assessed using two 24-h recalls and supplement questionnaires. PLP and PUFA concentrations were measured. Multivariate linear regression assessed the association of B6 intake and PLP with PUFA; multivariate logistic regression evaluated the relationship of adequate B6 status with high plasma PUFA, adjusting for demographic, socioeconomic, and dietary factors; physical activity; smoking; alcohol; medication; and BMI. There were interactions between gender and B6 intake on EPA (P-interaction = 0.008) and AA (P-interaction = 0.004) only, whereas no interaction existed between gender and PLP on PUFA. PLP was directly associated with EPA (β = 0.181, P = 0.002), DHA (β = 0.109, P = 0.005), EPA + DHA (β = 0.14, P = 0.002), EPA/AA (β = 0.186, P = 0.004), and (EPA + DHA)/AA (β = 0.13, P = 0.026). The odds of having high plasma EPA (adjusted (a) OR: 2.03, P = 0.049) and EPA/AA (aOR: 3.83, P < 0.0001) were greater in those with adequate B6 status compared to those with deficient B6 status. In conclusion, in US older adults, a higher PLP level was associated with a greater level of EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA. Adequate B6 status was associated with high EPA and EPA/AA status. These findings suggest that sufficient vitamin B6 status may positively influence PUFA metabolism in older adults.

The relationship between plasma free fatty acids, cognitive function and structural integrity of the brain in middle-aged healthy humans

Background: The cerebral composition of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) is believed to influence cognitive function and structural damage of the aging brain. However, existing data is inconsistent.Materials and Methods: This retrospective study explored the association between free plasma PUFA concentrations, cognitive function and brain structure atrophy in a well-characterized community-dwelling cohort of elderly individuals without stroke and dementia. Ten different fatty acids were analyzed in stored plasma samples from 391 non-demented elderly individuals by gas chromatography mass spectrometry. Neuropsychiatric tests capturing memory, executive function and visuopractical skills were performed in all participants. Brain atrophy was assessed by MRI in a subset of 167 individuals.Results: Higher plasma concentrations of free ω-6 PUFAs (p = 0.042), and, in particular, linoleic acid (p = 0.01), were significantly associated with lower executive function. No significant association existed between ω-3 PUFA concentrations and cognitive functioning. The volume of the frontal lobes was inversely associated with ω-6 PUFAs, whereas ω-3 PUFAs were positively related with temporal lobe volumes. All associations did not withstand correction for multiple comparisons.Conclusions: Our study suggests subtle effects of PUFA imbalances on cognition and brain structure. Yet the observed associations are weak and unlikely to be of clinical relevance. The brain regions that seem to be most sensitive to imbalances of ω-3 and ω-6 PUFAs are the frontal and temporal lobes.

Dietary intake and plasma levels of polyunsaturated fatty acids in early-stage Parkinson\u2019s disease

Polyunsaturated fatty acids (PUFA) are important for neuronal function and may contribute to the development of neurodegenerative diseases. Here, we investigated the correlation between dietary intake and plasma concentrations of PUFA and their associations with clinical severity in early-stage Parkinson’s disease (PD). In a case–control study with 38 patients with PD and 33 controls, we assessed dietary intake using food frequency questionnaires and simultaneously measured the plasma levels of five PUFA. No differences were observed in dietary total energy and lipid intake, including PUFA, between patients with PD and controls. However, α-linolenic acid (ALA), linoleic acid (LA), and arachidonic acid (AA) plasma levels were lower in patients with PD. The association between dietary intake and plasma PUFA concentrations was not significant in patients with PD. ALA and LA plasma levels were inversely correlated with motor severity in patients with PD, while docosahexaenoic acid and AA plasma levels were positively correlated with non-motor symptoms after controlling for age and sex.

Associations Between Vitamin B6 Status and Plasma Polyunsaturated Fatty Acids Among US Older Adults: NHANES 2003–2004

ObjectivesPrevious evidence suggests that vitamin B6 deficiency may have a deleterious impact on aging and the metabolism of polyunsaturated fatty acids (PUFA). However, the relationship of aging with vitamin B6 status and PUFA metabolism is poorly understood; population-based studies to assess the relationship between plasma pyridoxal 5′-phosphate (PLP; an active form of vitamin B6) and PUFA status for older adults are lacking. Thus, we examined the associations between plasma PLP concentration and plasma PUFA concentrations and ratios [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, and (EPA + DHA)/AA] among US older adults. We further investigated the association of adequate (PLP ≥ 20 nmol/L) versus deficient (PLP < 20 nmol/L) vitamin B6 status in those participants with plasma PUFA concentration above the median. MethodsA cross-sectional study analyzed 467 participants aged ≥60 years from the National Health and Nutrition Examination Survey (NHANES) 2003–2004. Nutrient intake data were estimated from two 24-h recalls and from questionnaires on the use of supplements. Plasma PLP and PUFA concentrations were measured. We used multivariable linear regression for obtaining unstandardized (b) and standardized (β) coefficients; multivariable logistic regression for adjusted odds ratios. Covariates included demographic, socioeconomic, dietary variables, physical activity, smoking, alcohol consumption, prescription medication use, and BMI. ResultsPlasma PLP was directly associated with plasma EPA (β = 0.176, b = 0.101, P = 0.002), DHA (β = 0.109, b = 0.046, P = 0.004), EPA + DHA (β = 0.137, b = 0.060, P = 0.002), EPA/AA (β = 0.169, b = 0.089, P = 0.009). The odds of having plasma EPA/AA and (EPA + DHA)/AA concentration above the median were greater in those with adequate vitamin B6 compared with those who were deficient [adjusted OR (aOR): 1.32, 95% CI: 0.8–2.17, P = 0.0001; aOR: 2.08, 95% CI: 1.0–4.33, P = 0.049, respectively]. ConclusionsIn US older adults, plasma PLP was directly associated with plasma EPA, DHA, EPA + DHA, EPA/AA. Adequate vitamin B6 status was associated with having above the median EPA/AA and (EPA + DHA)/AA. These findings suggest that adequate B6 status may positively influence PUFA metabolism in the older US population. Funding SourcesNo funding sources.

Gender Differences in the Associations of Plasma Pyridoxal 5'-Phosphate with Plasma Polyunsaturated Fatty Acids among US Young and Middle-Aged Adults: NHANES 2003-2004.

Vitamin B6-restricted diets and low plasma pyridoxal 5′-phosphate (PLP) status altered plasma polyunsaturated fatty acids (PUFA) compositions. Evidence suggests the role of gender in the metabolism of vitamin B6 and PUFA. However, no epidemiologic study examined the impact of gender on the relationship between vitamin B6 and PUFA status in adults. Thus, we investigated whether there were gender differences in the association of vitamin B6 intake and plasma PLP concentration with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, (EPA + DHA)/AA) in US young/middle-aged adults. In total, 864 participants (20–59 years; 484 men, 380 women) from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 were used for this cross-sectional study. Nutrient intakes were estimated from two 24 h recalls and supplement questionnaires; plasma PLP and PUFA were measured. Multivariate linear regression was utilized to obtain unstandardized (b) and standardized (β) coefficients. Covariates included demographic, socioeconomic, dietary variables, physical activity level, cigarette smoking status, alcohol consumption, prescription medication use, and BMI. There were significant interactions between gender and PLP on EPA (P-interaction = 0.004), DHA (P-interaction = 0.020), EPA + DHA (P-interaction = 0.010), EPA/AA (P-interaction = 0.002), (EPA + DHA)/AA (P-interaction = 0.004), whereas no interaction between gender and B6 intake existed. In gender-stratified analyses, in men, PLP was positively associated with EPA (β = 0.138, b = 0.104, p = 0.0004), DHA (β = 0.101, b = 0.058, p = 0.036), EPA + DHA (β = 0.125, b = 0.073, p = 0.005), EPA/AA (β = 0.144, b = 0.099, p = 0.0002), (EPA + DHA)/AA (β = 0.123, b = 0.068, p = 0.005). However, no associations between PLP and PUFA existed in women. In conclusion, gender differences were found in the relationships between plasma PLP and plasma EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA, with significant direct associations in men only among US young/middle-aged adults.

The effect of a duodenal-jejunal bypass liner on lipid profile and blood concentrations of long chain polyunsaturated fatty acids

Duodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs). Sub-study of a multicentre, randomised, controlled trial with two treatment groups. Patients aged 18-65 years with type-2 diabetes mellitus and body mass index 30-50kg/m2 were randomised to receive a DJBL for 12 months or best medical therapy, diet and exercise. Whole plasma PUFA concentrations were determined at baseline, 10 days, 6 and 11.5 months; data were available for n=70 patients per group. Weight loss was significantly greater in the DJBL group compared to controls after 11.5 months: total body weight loss 11.3±5.3% versus 6.0±5.7% (mean difference [95% CI]=5.27% [3.75, 6.80], p<0.001). Absolute concentrations of both EFAs, linoleic acid and α-linolenic acid, and their bioactive derivatives, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, were significantly lower in the DJBL group than in the control group at 6 and 11.5 months follow-up. Total serum cholesterol, LDL-cholesterol and HDL-cholesterol were also significantly lower in the DJBL group. One year of DJBL therapy is associated with superior weight loss and greater reductions in total serum cholesterol and LDL-cholesterol, but also depletion of EFAs and their longer chain derivatives. DJBL therapy may need to be offset by maintaining an adequate dietary intake of PUFAs or by supplementation. ClinicalTrials.gov Identifier NCT02459561.

Maternal polyunsaturated fatty acids and risk for autism spectrum disorder in the MARBLES high-risk study.

Prior studies suggest that maternal polyunsaturated fatty acids intake during pregnancy may have protective effects on autism spectrum disorder in their children. However, they did not examine detailed timing of maternal polyunsaturated fatty acid intake during pregnancy, nor did they evaluate plasma concentrations. This study investigates whether maternal polyunsaturated fatty acids in defined time windows of pregnancy, assessed by both questionnaires and biomarkers, are associated with risk of autism spectrum disorder and other non-typical development in the children. Food frequency questionnaires were used to estimate maternal polyunsaturated fatty acid intake during the first and second half of pregnancy. Gas chromatography measured maternal plasma polyunsaturated fatty acid concentrations in the third trimester. In all, 258 mother-child pairs from a prospective cohort were included. All mothers already had a child with autism spectrum disorder and were planning a pregnancy or pregnant with another child. Children were clinically assessed longitudinally and diagnosed at 36 months. For polyunsaturated fatty acid intake from questionnaires, we only found mothers consuming more omega-3 in the second half of pregnancy were 40% less likely to have children with autism spectrum disorder. For polyunsaturated fatty acid concentrations in the third-trimester plasma, we did not observe any statistical significance in relation to the risk of autism spectrum disorder. However, our study confirmed associations from previous studies between higher maternal docosahexaenoic acid and eicosapentaenoic acid plasma concentrations in the late pregnancy and reduced risk for non-typical development. This study markedly advanced understandings of whether and when maternal polyunsaturated fatty acid intake influences risk for autism spectrum disorder and sets the stage for prevention at the behavioral and educational level.

Comparing the plasma polyunsaturated fatty acid (PUFA) profile of beef cattle fed on different finishing diets

AbstractRed meat is an important dietary source of protein and many other essential nutrients including omega(n)-3 polyunsaturated fatty acids (PUFA) which provide numerous benefits to human health. It is well known that grass-fed meat contains a more favourable fatty acid profile, compared to other feeding regimes, but the feasibility of grass finishing is in decline for many farmers/producers. Therefore, alternative methods to enhance the fatty acid profile of red meats, such as beef, are needed to meet increasing consumer demands for ‘healthier’ products. This study compared plasma PUFA concentrations across cattle finished on three different feeding regimes. Three farms supplied livestock to the current study, where cattle were fed three different feeding regimes for a minimum of 15-weeks prior to slaughter. Feeding regimes were ad lib concentrate (negative control), n3-enriched ad lib concentrate (treatment) or grass-fed only (positive control). Blood was collected at slaughter into EDTA tubes and plasma aliquots were stored at -80°C until analysis. A validated gas chromatography–mass spectrometry (GC-MS) method was used to quantify individual PUFA concentrations in mg/ml [linoleic acid (LA); arachidonic acid (AA); alpha-linolenic acid (ALA); eicosapentaenoic acid (EPA); docosapentaenoic acid (DPA); docosahexaenoic acid (DHA)]. Samples from 23, 49 and 40 animals (in control, treatment &amp; grass groups, respectively) were available for the current analysis. One-way ANOVA tests revealed significant differences between groups in all PUFA concentrations quantified (all P &lt; 0.026). Post-hoc (LSD) tests showed mean ± SD n3 PUFA concentrations were significantly different within all three groups (all P &lt; 0.04), increasing from negative control (0.049 ± 0.013 mg/ml), to treatment (0.095 ± 0.034 mg/ml) and grass-fed groups (0.461 ± 0.132 mg/ml). The opposite was observed for mean ± SD n6 PUFA concentrations (1.060 ± 0.297 vs. 0.918 ± 0.267 vs. 0.355 ± 0.085 mg/ml, respectively; all P &lt; 0.02). Cattle finished on either treatment or grass regimes had a more favourable n6:n3 PUFA ratio, compared to negative control (11.98 and 0.79 vs. 22.65, respectively). This study demonstrates that the finishing diet can impact plasma PUFA concentrations of beef cattle. Animals finished on the n3-enriched concentrate had, on average, double the total n3 PUFA concentrations, as well as an improved n6:n3 ratio, compared to control cattle. These results provide preliminary data on an alternative n3-enriched feeding regime for beef cattle to improve PUFA concentrations. Further research, however, is required to confirm if such beneficial changes are also observed in bovine muscle, which would have direct benefits for consumers.

The Association between Plasma Omega-6/Omega-3 Ratio and Anthropometric Traits Differs by Racial/Ethnic Groups and NFKB1 Genotypes in Healthy Young Adults.

Evidence for a relationship between omega-6/omega-3 (n-6/n-3) polyunsaturated fatty acid (PUFA) ratio and obesity in humans is inconsistent, perhaps due to differences in dietary intake or metabolism of PUFAs between different subsets of the population. Since chronic inflammation is central to obesity and inflammatory pathways are regulated by PUFAs, the objective of this study was to examine whether variants in the NFKB1 gene, an upstream regulator of the inflammatory response, modify the association between the n-6/n-3 ratio (from diet and plasma) and anthropometric traits in a multiethnic/multiracial population of young adults. Participants’ (n = 898) dietary PUFA intake was assessed using a food frequency questionnaire and plasma PUFA concentrations by gas chromatography. Nine tag single nucleotide polymorphisms (SNP) in NFKB1 were genotyped. Significant interactions were found between racial/ethnic groups and plasma n-6/n-3 ratio for body mass index (BMI) (p = 0.02) and waist circumference (WC) (p = 0.007). Significant interactions were also observed between racial/ethnic groups and three NFKB1 genotypes (rs11722146, rs1609798, and rs230511) for BMI and WC (all p ≤ 0.04). Significant interactions were found between two NFKB1 genotypes and plasma n-6/n-3 ratio for BMI and WC (rs4648090 p = 0.02 and 0.03; rs4648022 p = 0.06 and 0.04, respectively). Our findings suggest that anthropometric traits may be influenced by a unique combination of n-6/n-3 ratio, racial/ethnic background, and NFKB1 genotypes.

Higher Waist Circumference Is Related to Lower Plasma Polyunsaturated Fatty Acids in Healthy Participants: Metabolic Implications

Objective: We evaluated whether the relationship between waist circumference (WC) and cardiometabolic risk is related to usual diet and plasma fatty acid composition.Methods: This cross-sectional study included 226 health professionals from 20 to 59 years old. Anthropometric features, oxidative stress, inflammatory markers, and plasma fatty acid profile were assessed. Dietary intake was evaluated with a semi-quantitative food frequency questionnaire, the quality of dietary habits by Healthy Eating Index, and insulin resistance by homeostasis model assessment–insulin resistance and triglyceride-glucose index.Results: Higher WC was associated with lower concentrations of high-density lipoprotein cholesterol (p = 0.000) and adiponectin (p = 0.000) and higher uric acid levels (p = 0.011). Plasma polyunsaturated fatty acid (PUFA) levels were negatively associated with weight (p = 0.046), systolic blood pressure (p = 0.035), fasting glucose (p = 0.000), triglyceride-glucose index (p = 0.023), and IL-1β (p = 0.037). Individuals with elevated WC consumed more calories (p = 0.002), niacin (p = 0.002), and pyridoxine (p = 0.017), but less calcium (p = 0.001), phosphorus (p = 0.016), and vitamin B2 (p = 0.011). In addition, individuals with higher WC denoted lower PUFA concentrations (p = 0.036).Conclusion: The results suggest that participants with higher WC have lower plasma PUFA concentrations and higher levels of saturated fatty acids. This could be related to metabolic and inflammatory changes that could trigger increased risk of metabolic syndrome and cardiovascular disease.

A regulatory insertion-deletion polymorphism in the FADS gene cluster influences PUFA and lipid profiles among Chinese adults: a population-based study

Arachidonic acid (AA) is the major polyunsaturated fatty acid (PUFA) substrate for potent eicosanoid signaling to modulate inflammation and thrombosis and is controlled in part by tissue abundance. Fatty acid desaturase 1 (FADS1) catalyzes synthesis of omega-6 (n-3) AA and n-3 eicosapentaenoic acid (EPA). The rs66698963 polymorphism, a 22-base pair (bp) insertion-deletion 137 bp downstream of a sterol regulatory element in FADS2 intron 1, mediates expression of FADS1 in vitro, as well as exerting positive selection in several human populations. The associations between the polymorphism rs66698963 and plasma PUFAs as well as disease phenotypes are unclear. This study aimed to evaluate the relation between rs66698963 genotypes and plasma PUFA concentrations and blood lipid profiles. Plasma fatty acids were measured from a single sample obtained at baseline in 1504 healthy Chinese adults aged between 35 and 59 y with the use of gas chromatography. Blood lipids were measured at baseline and a second time at the 18-mo follow-up. The rs66698963 genotype was determined by using agarose gel electrophoresis. Linear regression and logistic regression analyses were performed to assess the association between genotype and plasma PUFAs and blood lipids. A shift from the precursors linoleic acid and α-linolenic acid to produce AA and EPA, respectively, was observed, consistent with FADS1 activity increasing in the order of genotypes D/D to I/D to I/I. For I/I compared with D/D carriers, plasma concentrations of n-6 AA and the ratio of AA to n-3 EPA plus docosahexaenoic acid (DHA) were 57% and 32% higher, respectively. Carriers of the deletion (D) allele of rs66698963 tended to have higher triglycerides (β=0.018; SE: 0.009; P=0.05) and lower HDL cholesterol (β=-0.008; SE: 0.004; P=0.02) than carriers of the insertion (I) allele. The rs66698963 genotype is significantly associated with AA concentrations and AA to EPA+DHA ratio, reflecting basal risk of inflammatory and related chronic disease phenotypes, and is correlated with the risk of dyslipidemia. This trial was registered at chictr.org.cn as ChiCTR-EOC-17012759.

Maternal Fatty Acid Status During Pregnancy and Child Autistic Traits: The Generation R Study.

ω-3 and ω-6 polyunsaturated fatty acids are important for brain function and development. We examined whether maternal polyunsaturated fatty acid status during pregnancy affects risk of autistic traits in childhood. Within the Generation R cohort, we measured maternal plasma polyunsaturated fatty acid concentrations and the ω-3:ω-6 ratio in midpregnancy (Rotterdam, the Netherlands, 2001-2005). Child autistic traits at 6 years were assessed by using the Social Responsiveness Scale short form in 4,624 children. A lower maternal ω-3:ω-6 ratio during pregnancy was associated with more autistic traits in the offspring (β = -0.008, 95% confidence interval: -0.016, -0.001). In particular, a higher total ω-6 and linoleic acid status were associated with more autistic traits (all P's < 0.05). Associations were independent of child intelligence, suggesting that the fatty acid distribution specifically affects the development of autistic traits in addition to general neurodevelopment. Maternal plasma ω-3 status was not associated with child autistic traits and, consistently, neither was prenatal dietary fish intake. Our study shows that a lower prenatal ω-3:ω-6 ratio is associated with more child autistic traits, which is largely accounted for by higher ω-6 instead of lower ω-3 status. These results suggest a biological pathway between maternal fatty acid intake during pregnancy and autistic traits in the offspring.

Maternal plasma PUFA concentrations during pregnancy and childhood adiposity: the Generation R Study1–3

Maternal polyunsaturated fatty acid (PUFA) concentrations during pregnancy may have persistent effects on growth and adiposity in the offspring. A suboptimal maternal diet during pregnancy might lead to fetal cardiometabolic adaptations with persistent consequences in the offspring. We examined the associations of maternal PUFA concentrations during pregnancy with childhood general and abdominal fat-distribution measures. In a population-based, prospective cohort study of 4830 mothers and their children, we measured maternal second-trimester plasma n-3 (ω-3) and n-6 (ω-6) PUFA concentrations. At the median age of 6.0 y (95% range: 5.6, 7.9 y), we measured childhood body mass index (BMI), the fat mass percentage, and the android:gynoid fat ratio with the use of dual-energy X-ray absorptiometry and measured the preperitoneal abdominal fat area with the use of ultrasound. Analyses were adjusted for maternal and childhood sociodemographic- and lifestyle-related characteristics. We observed that higher maternal total n-3 PUFA concentrations, and specifically those of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid, were associated with a lower childhood total-body fat percentage and a lower android:gynoid fat mass ratio (P< 0.05) but not with childhood BMI and the abdominal preperitoneal fat mass area. Higher maternal total n-6 PUFA concentrations, and specifically those of dihomo-γ-linolenic acid, were associated with a higher childhood total-body fat percentage, android:gynoid fat mass ratio, and abdominal preperitoneal fat mass area (P< 0.05) but not with childhood BMI. In line with these findings, a higher maternal n-6:n-3 PUFA ratio was associated with higher childhood total-body and abdominal fat mass. Lower maternal n-3 PUFA concentrations and higher n-6 PUFA concentrations during pregnancy are associated with higher body fat and abdominal fat in childhood. Additional studies are needed to replicate these observations and to explore the causality, the underlying pathways, and the long-term cardiometabolic consequences.

Plasma concentrations of trans fatty acids in persons with type 2 diabetes between September 2002 and April 2004

transFatty acids (TFAs) increase cardiovascular disease risk. TFAs and polyunsaturated fatty acids (PUFAs) in the food supply may be declining with reciprocal increases in cis-monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs). We sought to determine whether plasma 18-carbon TFA and PUFA concentrations might decrease over time and whether there might be reciprocal increases in plasma cis-MUFAs and SFAs. We studied 305 persons (171 women) taking part in Look AHEAD (Action for Health in Diabetes), a randomized trial of lifestyle intervention for weight loss to reduce major cardiovascular events in overweight and obese adults (aged 45-76 y) with type 2 diabetes who also participated in an ancillary study of oxidative stress. This study was a cross-sectional analysis of TFAs, cis-MUFAs, SFAs, and PUFAs measured in plasma before intervention (September 2002-April 2004). In a model that included demographic characteristics, plasma total fatty acid concentration, BMI, serum insulin, statin use, season, and longitudinal time trend (R(2) = 0.167, P < 0.0001), plasma TFAs decreased by 13.5%/y (95% CI: -22.7, -3.2%/y; absolute decrease 7.0 mg · L(-1) · y(-1); 95% CI: -12.5, -1.6 mg · L(-1) · y(-1); P = 0.012). This longitudinal trend was not significantly altered by further adjustment for dietary variables and physical activity. In contrast, longitudinal trends for PUFAs, cis-MUFAs, and SFAs were weak and not significant. This change in plasma concentrations of TFAs is consistent with changes in fatty acid composition that food manufacturers are likely to have made to avoid declaring TFAs on food labels. Further research will be needed to determine the overall effect of these changes on cardiovascular risk. The Look AHEAD trial is registered at clinicaltrials.govas NCT00017953.

Maternal plasma polyunsaturated fatty acid status in late pregnancy is associated with offspring body composition in childhood.

Maternal diet during pregnancy has been linked to offspring adiposity, but it is unclear whether maternal polyunsaturated fatty acid (PUFA) status during pregnancy affects offspring body composition. We investigated the associations between maternal plasma n-3 and n-6 PUFA status at 34 wk gestation and offspring body composition. A prospective United Kingdom population-based mother-offspring cohort, the Southampton Women's Survey (SWS), was studied. A total of 12,583 nonpregnant women were recruited into the SWS, among whom 1987 delivered a baby before December 31, 2003; 293 mother-child pairs had complete measurements of maternal plasma PUFA concentrations in late pregnancy and offspring body composition at both ages 4 and 6 yr. We measured offspring body composition by dual-energy x-ray absorptiometry, yielding fat mass, lean mass, percentage fat mass, and percentage lean mass. Results are presented as β-coefficients for standardized variables, therefore reflecting the sd change of the outcome for every 1 sd of the predictor. After adjustment for maternal factors and child factors including height and duration of breast-feeding, maternal plasma n-6 PUFA concentration positively predicted offspring fat mass at 4 yr (β = 0.14 SD/SD; P = 0.01) and 6 yr (β = 0.11 SD/SD; P = 0.04), but there was no association with offspring lean mass at either age (β = 0.005 SD/SD, P = 0.89; and β = 0.008 SD/SD, P = 0.81, respectively). Maternal plasma n-3 PUFA concentration was not associated with offspring fat mass at 4 yr (β = 0.057 SD/SD; P = 0.34) or 6 yr (β = 0.069 SD/SD; P = 0.21). Maternal plasma n-3 PUFA status was positively associated with offspring lean mass on univariate analysis (4 yr, β = 0.11, P = 0.06; 6 yr, β = 0.14; P = 0.02); however, this was confounded by a positive association with offspring height. This observational study suggests that maternal n-6 PUFA status during pregnancy might influence offspring adiposity in childhood.

Prenatal fatty acid status and child adiposity at age 3 y: results from a US pregnancy cohort

Exposure to polyunsaturated fatty acids (PUFAs) in early life may influence adiposity development. We examined the extent to which prenatal n-3 (omega-3) and n-6 (omega-6) PUFA concentrations were associated with childhood adiposity. In mother-child pairs in the Project Viva cohort, we assessed midpregnancy fatty acid intakes (n = 1120), maternal plasma PUFA concentrations (n = 227), and umbilical cord plasma PUFA concentrations (n = 302). We performed multivariable regression analyses to examine independent associations of n-3 PUFAs, including docosahexaenoic and eicosapentaenoic acids (DHA + EPA), n-6 PUFAs, and the ratio of n-6:n-3 PUFAs, with child adiposity at age 3 y measured by the sum of subscapular and triceps skinfold thicknesses (SS + TR) and risk of obesity (body mass index ≥95th percentile for age and sex). Mean (±SD) DHA + EPA intake was 0.15 ± 0.14 g DHA + EPA/d, maternal plasma concentration was 1.9 ± 0.6%, and umbilical plasma concentration was 4.6 ± 1.2%. In children, SS + TR was 16.7 ± 4.3 mm, and 9.4% of children were obese. In the adjusted analysis, there was an association between each SD increase in DHA + EPA and lower child SS + TR [-0.31 mm (95% CI: -0.58, -0.04 mm) for maternal diet and -0.91 mm (95% CI: -1.63, -0.20 mm) for cord plasma] and lower odds of obesity [odds ratio (95% CI): 0.68 (0.50, 0.92) for maternal diet and 0.09 (0.02, 0.52) for cord plasma]. Maternal plasma DHA + EPA concentration was not significantly associated with child adiposity. A higher ratio of cord plasma n-6:n-3 PUFAs was associated with higher SS + TR and odds of obesity. An enhanced maternal-fetal n-3 PUFA status was associated with lower childhood adiposity.

Validation of a Food Frequency Questionnaire to Assess Intake of n-3 Polyunsaturated Fatty Acids in Subjects with and without Major Depressive Disorder

The role of n-3 polyunsaturated fatty acids (PUFAs) in psychiatric illness is a topic of public health importance. This report describes development and biomarker validation of a 21-item, self-report food frequency questionnaire (FFQ) intended for use in psychiatric research to assess intake of α-linolenic acid (18:3n-3 [ALA]), docosahexaenoic acid (22:6n-3 [DHA]), and eicosapentaenoic acid (20:5n-3 [EPA]). In a cross-sectional study conducted from September 2006 to September 2008, sixty-one ethnically diverse adult participants with (n=34) and without (n=27) major depressive disorder completed this n-3 PUFA FFQ and provided a plasma sample. Plasma levels of n-3 PUFAs EPA and DHA, and n-6 PUFA arachidonic acid (20:4n-6 [AA]) were quantified by gas chromatography. Using Spearman's ρ, FFQ-estimated intake correlated with plasma levels of DHA ( r=0.50; P<0.0001) and EPA ( r=0.38; P=0.002), but not with ALA levels ( r=0.22; P=0.086). Participants were classified into quartiles by FFQ-estimated intake and plasma PUFA concentrations. Efficacy of the FFQ to rank individuals into same or adjacent plasma quartiles was 83% for DHA, 78.1% for EPA, and 70.6% for ALA; misclassification into extreme quartiles was 4.9% for DHA, 6.5% for EPA, and 8.2% for ALA. FFQ-estimated EPA intake and plasma EPA were superior to plasma AA levels as predictors of the plasma AA to EPA ratio. This brief FFQ can provide researchers and clinicians with valuable information concerning dietary intake of DHA and EPA.