Dietary Intake Of Linoleic Acid Research Articles

Linoleic acid improves assembly of the CII subunit and CIII2/CIV complex of the mitochondrial oxidative phosphorylation system in heart failure

BackgroundLinoleic acid is the major fatty acid moiety of cardiolipin, which is central to the assembly of components involved in mitochondrial oxidative phosphorylation (OXPHOS). Although linoleic acid is an essential nutrient, its excess intake is harmful to health. On the other hand, linoleic acid has been shown to prevent the reduction in cardiolipin content and to improve mitochondrial function in aged rats with spontaneous hypertensive heart failure (HF). In this study, we found that lower dietary intake of linoleic acid in HF patients statistically correlates with greater severity of HF, and we investigated the mechanisms therein involved.MethodsHF patients, who were classified as New York Heart Association (NYHA) functional class I (n = 45), II (n = 93), and III (n = 15), were analyzed regarding their dietary intakes of different fatty acids during the one month prior to the study. Then, using a mouse model of HF, we confirmed reduced cardiolipin levels in their cardiac myocytes, and then analyzed the mechanisms by which dietary supplementation of linoleic acid improves cardiac malfunction of mitochondria.ResultsThe dietary intake of linoleic acid was significantly lower in NYHA III patients, as compared to NYHA II patients. In HF model mice, both CI-based and CII-based OXPHOS activities were affected together with reduced cardiolipin levels. Silencing of CRLS1, which encodes cardiolipin synthetase, in cultured cardiomyocytes phenocopied these events. Feeding HF mice with linoleic acid improved both CI-based and CII-based respiration as well as left ventricular function, together with an increase in cardiolipin levels. However, although assembly of the respirasome (i.e., CI/CIII2/CIV complex), as well as assembly of CII subunits and the CIII2/CIV complex statistically correlated with cardiolipin levels in cultured cardiomyocytes, respirasome assembly was not notably restored by dietary linoleic acid in HF mice. Therefore, although linoleic acid may significantly improve both CI-based and CII-based respiration of cardiomyocytes, respirasomes impaired by HF were not easily repaired by the dietary intake of linoleic acid.ConclusionsDietary supplement of linoleic acid is beneficial for improving cardiac malfunction in HF, but is unable to completely cure HF.

Comparisons of Estimated Intakes and Plasma Concentrations of Selected Fatty Acids in Pregnancy.

The growing interest in potential health effects of long-chain polyunsaturated fatty acids (PUFAs) makes it important to evaluate the method used to assess the fatty acid intake in nutrition research studies. We aimed to validate the questionnaire-based dietary intake of selected PUFAs: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), α-linolenic acid (ALA), linoleic acid (LA), and arachidonic acid (AA) within the Danish National Birth Cohort (DNBC), by comparing 345 women’s reported intake with concentration of plasma biomarkers. The applied questionnaire- and biomarker data reflect dietary intake from around the same time point in mid-pregnancy and relationships were investigated by use of Pearson and Spearman correlation and linear regression statistics. We demonstrated moderate but consistent adjusted correlations between dietary intake estimates and the corresponding plasma biomarker concentrations (differences in plasma concentration per 100 mg/day greater intake of 0.05 (95% CI: 0.02; 0.08)) and 0.05 (95% CI: 0.01; 0.08) percentage of total plasma fatty acids for EPA and DHA, respectively). The associations strengthened when restricting the analyses to women with ALA intake below the median intake. We found a weak correlation between the dietary intake of ALA and its plasma biomarker with a difference in plasma concentration of 0.07 (95% CI: 0.03; 0.10) percent of total plasma fatty acids per 1 g/day greater intake, while the dietary intake of LA and AA did not correlate with their corresponding biomarkers.

Inflammatory response to dietary linoleic acid depends on FADS1 genotype

The health benefits of substituting dietary polyunsaturated fatty acids (PUFAs) for saturated fatty acids are well known. However, limited information exists on how the response to dietary intake of linoleic acid (LA; 18:2n-6) is modified by polymorphisms in the fatty acid desaturase (FADS) gene cluster. The aim of the current study was to test the hypothesis that the FADS1 rs174550 genotype modifies the effect of dietary LA intake on the fatty acid composition of plasma lipids, fasting glucose, and high-sensitivity C-reactive protein (hsCRP). Associations were investigated between genotype, plasma PUFAs, fasting glucose, and hsCRP concentrations in the cross-sectional, population-based Metabolic Syndrome in Men cohort (n=1337). In addition, 62 healthy men from the cohort who were homozygotes for the TT or CC genotype of the FADS1 rs174550 were recruited to a 4-wk intervention (FADSDIET) with an LA-enriched diet. The fatty acid composition of plasma PUFAs and concentrations of plasma fasting glucose, serum hsCRP, and plasma lipid mediators (eicosanoids and related analogs) were measured at the beginning and end of the 4-wk intervention period. In the FADSDIET trial, the plasma LA proportion increased in both genotype groups in response to an LA-enriched diet. Responses in concentrations of serum hsCRP and plasma fasting glucose and the proportion of arachidonic acid (20:4n-6) in plasma phospholipids and cholesteryl esters differed between genotype groups (interaction of diet × genotype, P<0.05). In TT homozygous subjects, plasma eicosanoid concentrations correlated with the arachidonic acid proportion in plasma and with hsCRP (r=0.4-0.7, P<0.05), whereas in the CC genotype there were no correlations. Our findings show that the FADS1 genotype modifies metabolic responses to dietary LA. The emerging concept that personalized dietary counseling should be modified by the FADS1 genotype needs to be tested in larger randomized trials. The study was registered at clinicaltrials.gov as NCT02543216.

Low-linoleic acid diet and oestrogen enhance the conversion of α-linolenic acid into DHA through modification of conversion enzymes and transcription factors.

Conversion of α-linolenic acid (ALA) into the longer chain n-3 PUFA has been suggested to be affected by the dietary intake of linoleic acid (LA), but the mechanism is not well known. Therefore, the purpose of this study was to evaluate the effect of a low-LA diet with and without oestrogen on the fatty acid conversion enzymes and transcription factors. Rats were fed a modified American Institute of Nutrition-93G diet with 0% n-3 PUFA or ALA, containing low or high amounts of LA for 12 weeks. At 8 weeks, the rats were injected with maize oil with or without 17β-oestradiol-3-benzoate (E) at constant intervals for the remaining 3 weeks. Both the low-LA diet and E significantly increased the hepatic expressions of PPAR-α, fatty acid desaturase (FADS) 2, elongase of very long chain fatty acids 2 (ELOVL2) and ELOVL5 but decreased sterol regulatory element binding protein 1. The low-LA diet, but not E, increased the hepatic expression of FADS1, and E increased the hepatic expression of oestrogen receptor-α and β. The low-LA diet and E had synergic effects on serum and liver levels of DHA and on the hepatic expression of PPAR-α. In conclusion, the low-LA diet and oestrogen increased the conversion of ALA into DHA by upregulating the elongases and desaturases of fatty acids through regulating the expression of transcription factors. The low-LA diet and E had a synergic effect on serum and liver levels of DHA through increasing the expression of PPAR-α.

Abstract P225: The Associations of Dietary and Biomarkers of Linoleic Acid Intake and All-cause and Cardiovascular Mortality: A Systematic Review and Meta-analysis

Background: Previous studies on intake of linoleic acid (LA), a predominant n-6 fatty acid, and risk of mortality from all-cause and cardiovascular disease (CVD) have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of LA and all-cause and CVD mortality. Methods: We searched MEDLINE and EMBASE databases through June 2017 for prospective cohort studies reporting association of LA (assessed by dietary survey or biomarker in blood or adipose tissue) with all-cause and CVD mortality. In addition, unpublished data from pooling projects were included. We pooled the multivariate-adjusted Hazards ratios (HRs) using random-effect meta-analysis, which allowed for between-study heterogeneity. Results: 27 studies covering 37 prospective cohorts were identified; these included 274,565 individuals with dietary assessment (34,597 all-cause and 10,636 CVD deaths) and 54,794 individuals with biomarker measurements (6,767 all-cause and 5,311 CVD deaths). Comparing the highest category with the lowest, dietary LA intake was associated with a 14% lower risk of all-cause mortality (95% confidence interval [CI], 2%-25%, I 2 =71%) and a 20% lower risk of CVD mortality (95% CI, 13%-26%, I 2 =0). Baseline health status (i.e. general population, CVD/high risk for CVD, or cancer) might be a main source of heterogeneity for the association of dietary LA intake with all-cause mortality. As for biomarkers, 1 SD increment in LA was associated with a 9% lower risk of all-cause mortality (95% CI, 4%-14%, I 2 =61%) and a 10% lower risk of CVD mortality (95% CI, 5%-14%, I 2 =13%). Heterogeneity was presented across tissue types and between genders. Conclusions: In prospective cohort studies, LA intake, assessed by either dietary survey or biomarkers, was inversely associated with all-cause and CVD mortality in a dose-response manner. These data support the current recommendations on polyunsaturated fat intake for prevention of CVD and early death.

Dietary linoleic acid interacts with FADS1 genetic variability to modulate HDL-cholesterol and obesity-related traits

Blood levels of polyunsaturated fatty acids (PUFAs) are under control of endogenous synthesis via Δ5- and Δ6-desaturases, encoded by the FADS1 and FADS2 genes, respectively and of diet. Genome-wide associations studies (GWAS) reported associations between polymorphisms in FADS1-FADS2 and variations in plasma concentrations of PUFAs, HDL- and LDL-cholesterol and triglycerides. However, it is not established whether dietary PUFAs intake modulates these associations. We assessed whether dietary linoleic acid (LA) or α-linolenic acid (ALA) modulate the association between the FADS1 rs174547 polymorphism (a GWAS hit) and lipid and anthropometric phenotypes. Dietary intakes of LA and ALA, FADS1 rs174547 genotypes, lipid and anthropometric variables were determined in three French population-based samples (n=3069). These samples were stratified according to the median dietary LA (<9.5 and ≥9.5g/d) and ALA (<0.80 and ≥0.80g/d) intakes. The meta-analysis was performed using a random-effect. Our meta-analysis confirmed the association between rs174547 and plasma lipid levels and revealed an association with waist circumference and body mass index. These associations were not modified by dietary ALA intake (all p-interaction>0.05). In contrast, the associations with HDL-cholesterol levels, waist circumference and BMI were modulated by the dietary intake of LA (p interaction<0.05). In high LA consumers only, the rs174547 minor allele was significantly associated with lower HDL-cholesterol levels (β=-0.05mmol/L, p=0.0002). Furthermore, each copy of the rs174547 minor allele was associated with a 1.58cm lower waist circumference (p=0.0005) and a 0.46kgm-2 lower BMI (p=0.01) in the low LA intake group, but not in the high LA intake group. The present study suggests that dietary LA intake may modulate the association between the FADS gene variants and HDL-cholesterol concentration, waist circumference and BMI. These gene-nutrient interactions, if confirmed, suggest that subjects carrying the rs174547 minor allele might benefit from low dietary LA intakes.

Comparative effects of high oleic acid vs high mixed saturated fatty acid obesogenic diets upon PUFA metabolism in mice

Emerging evidence indicates that the fatty acid composition of obesogenic diets influences physiologic outcomes. There are scant data regarding how the content of non-essential fatty acids like monounsaturated fatty acids (MUFA) and saturated fatty acids (SFAs) impact the metabolism of polyunsaturated fatty acids (PUFAs). In this work, we tested the hypothesis that obesogenic diets enriched in oleic acid (OA; 18:1n-9) reduce polyunsaturated fatty acid (PUFA) levels vs an obesogenic diet enriched in SFAs. Adult male mice were fed for eight weeks either (1) a control 16% fat energy (en) diet with 5.7% en OA and 4.4% en SFA, (2) a 50% fat en diet with 33% en OA and 9.9% en SFA, or (3) a 50% en diet with a high SFA diet with 33% en SFA and 9.1% en OA. Dietary levels and intake of linoleic acid (LA; 18:2n-6) and α-linolenic acid (ALA; 18:3n-3) were constant between the experimental groups. Several peripheral organs (liver, heart, kidney, and adipose) were analyzed for lipid composition and oxylipin analysis was performed for liver and adipose. Our data demonstrate that a high OA diet reduced tissue content of LA and ALA (≥30%) in phospholipid and neutral lipid fractions, reduced the content of some LA-derived and ALA-derived oxylipins in liver and adipose, and conversely, elevated hepatic content of PGF2α. In all tissues examined, except for adipose, levels of arachidonic acid (ARA; 20:4n-6) and docosahexaenoic acid (DHA; 22:6n-3) were either elevated or unaffected by the obesogenic diets. Our data indicate that the non-essential fatty content of obesogenic diets impacts PUFA content in peripheral tissues and influences the levels of bioactive oxylipins.

Dietary linoleic acid intake and blood inflammatory markers: a systematic review and meta-analysis of randomized controlled trials.

The aim of the present study was to investigate the effect of increasing dietary linoleic acid (LA) intake on the blood concentrations of inflammatory markers including cytokines, acute phase reactants and adhesion molecules in adults. We comprehensively searched PubMed, Embase and Cochrane Library for eligible studies. Overall, 30 randomized controlled studies involving 1377 subjects were included for meta-analysis. No significant effect of higher LA intake was observed for cytokines: tumor necrosis factor (SMD: -0.01; 95% CI: -0.19 to 0.17), interleukin-6 (SMD: 0.11, 95% CI: -0.07 to 0.29), adiponectin (SMD: 0.17, 95% CI: -0.17 to 0.50) and monocyte chemoattractant protein 1 (SMD: 0.14, 95% CI: -0.33 to 0.60). Pooled effect size from 16 studies showed that the C-reactive protein (CRP) concentration was not significantly affected by increasing LA intake (SMD = 0.09, 95% CI: -0.05 to 0.24). However, subgroup and meta-regression analysis suggested that in subjects with a more profound increase of dietary LA intake, LA might increase the blood CRP level. Other acute phase reactants including fibrinogen and plasminogen activator inhibitor-1 and adhesion molecules were not significantly changed when LA was increased in diet. No significant heterogeneity or publication bias was observed, although only a limited number of eligible studies were included for some markers. Our meta-analysis suggested that increasing dietary LA intake does not have a significant effect on the blood concentrations of inflammatory markers. However, the extent of change in dietary LA intake might affect the effect of LA supplementation on CRP.

Bipolar disorder moderates associations between linoleic acid and markers of inflammation

Dietary polyunsaturated fatty acids (PUFA) and inflammatory proteins associate with immune activation and have been implicated in the pathophysiology of mood disorders. We have previously reported that individuals with bipolar disorder (BPD) have decreased PUFA intake, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA); and decreased PUFA concentration of plasma EPA and linoleic acid (LA). We have also reported an association between plasma LA and its metabolites and burden of disease measures in BPD. In the current cross-sectional study we collected blood samples and diet records from both bipolar (n = 91) and control subjects (n = 75) to quantify plasma cytokine concentrations and dietary LA intake, respectively. Using multiple linear regression techniques, we tested for case control differences in plasma cytokine levels and associations between cytokines and dietary LA intake, adjusting for sex, age, BMI, and total energy intake. We found significantly higher plasma levels of interleukin 18 (IL-18) (p = 0.036), IL-18 binding protein (IL-18BP) (p = 0.001), soluble tumor necrosis factor receptor (sTNFR) 1 (p = 0.006), and sTNFR2 (p = 0.007) in BPD compared with controls. Moreover, BPD significantly moderated the associations of dietary LA intake with plasma levels of IL-18, sTNFR1 and sTNFR2, which were inverse associations in bipolar individuals and positive associations in controls (p for dietary LA x BPD diagnosis interaction < 0.05 for all three). These findings suggest potential dysregulation of LA metabolism in BPD, which may extend to a modified influence of dietary LA on specific inflammatory pathways in individuals with BPD compared to healthy controls.

Reducing dietary intake of linoleic acid of mouse dams during lactation increases offspring brain n-3 LCPUFA content

Omega (n-)3 and n-6 long chain polyunsaturated fatty acids (LCPUFA) accumulation in the infant brain after birth is strongly driven by dietary supply of n-3 and n-6 LCPUFAs and their C18 precursors through breast milk or infant formula. n-3 LCPUFA accretion is associated with positive effects on neurodevelopmental outcome whereas high n-6 LCPUFA accumulation is considered disadvantageous. Maternal diet is crucial for breast milk fatty acid composition. Unfortunately, global increases in linoleic acid (C18:2n-6; LA) intake have dramatically increased n-6 LCPUFA and reduced n-3 LCPUFA availability for breastfed infants. We investigated the effects of reducing maternal dietary LA, or increasing n-3 LCPUFA, during lactation on milk and offspring brain fatty acids in mice. Offspring brain n-3 LCPUFA was higher following both interventions, although effects were mediated by different mechanisms. Because of competitive interactions between n-3 and n-6 fatty acids, lowering maternal LA intake may support neurodevelopment in breastfed infants.

Essential fatty acid supplementation during lactation is required to maximize the subsequent reproductive performance of the modern sow

This study was conducted to investigate the effects of supplemental essential fatty acids (EFA) on sow reproductive efficiency and to estimate the concentrations of EFA required by the lactating sow for maximum subsequent reproduction. Data were collected on 480 sows (PIC Camborough) balanced by parity, with 241 and 239 sows representing Parity 1, and 3–5 (P3+), respectively. Sows were assigned randomly, within parity, to a 3×3 factorial arrangement plus a control diet without added lipids. Factors included linoleic (2.1%, 2.7%, and 3.3%) and α-linolenic acid (0.15%, 0.30%, and 0.45%), obtained by adding 4% of different mixtures of canola, corn and flaxseed oils to diets. Diets were corn-soybean meal based with 12% wheat middlings. The benefits of supplemental EFA were more evident for the subsequent reproduction of mature P3+ sows. For these sows, supplemental α-linolenic acid improved the proportion of sows that farrowed relative to sows weaned (linear P=0.080; 82.8, 80.5, and 92.8% for sows fed 0.15%, 0.30%, and 0.45% α-linolenic acid, respectively). In addition, supplemental linoleic acid, fed to Parity 1 and P3+ sows, tended to increase subsequent litter size (linear P=0.074; 13.2, 13.8 and 14.0 total pigs born for 2.1%, 2.7% and 3.3% linoleic acid, respectively). These results demonstrate that a minimum dietary intake of both α-linolenic and linoleic acid is required for the modern lactating sow to achieve a maximum reproductive outcome through multiple mechanisms that include rapid return to estrus, increased maintenance of pregnancy and improved subsequent litter size.

Malondialdehyde induces autophagy dysfunction and VEGF secretion in the retinal pigment epithelium in age-related macular degeneration

Age-related macular degeneration (AMD) is a major cause of blindness in developed countries and is closely related to oxidative stress, which leads to lipid peroxidation. Malondialdehyde (MDA) is a major byproduct of polyunsaturated fatty acid (PUFA) peroxidation. Increased levels of MDA have been reported in eyes of AMD patients. However, little is known about the direct relationship between MDA and AMD. Here we show the biological importance of MDA in AMD pathogenesis. We first confirmed that MDA levels were significantly increased in eyes of AMD patients. In ARPE-19 cells, a human retinal pigment epithelial cell line, MDA treatment induced vascular endothelial growth factor (VEGF) expression alternation, cell junction disruption, and autophagy dysfunction that was also observed in eyes of AMD patients. The MDA-induced VEGF increase was inhibited by autophagy–lysosomal inhibitors. Intravitreal MDA injection in mice increased laser-induced choroidal neovascularization (laser-CNV) volumes. In a mouse model fed a high-linoleic acid diet for 3 months, we found a significant increase in MDA levels, autophagic activity, and laser-CNV volumes. Our study revealed an important role of MDA, which acts not only as a marker but also as a causative factor of AMD pathogenesis-related autophagy dysfunction. Furthermore, higher dietary intake of linoleic acid promoted CNV progression in mice with increased MDA levels.

Increase in adipose tissue linoleic acid of US adults in the last half century.

Linoleic acid (LA) is a bioactive fatty acid with diverse effects on human physiology and pathophysiology. LA is a major dietary fatty acid, and also one of the most abundant fatty acids in adipose tissue, where its concentration reflects dietary intake. Over the last half century in the United States, dietary LA intake has greatly increased as dietary fat sources have shifted toward polyunsaturated seed oils such as soybean oil. We have conducted a systematic literature review of studies reporting the concentration of LA in subcutaneous adipose tissue of US cohorts. Our results indicate that adipose tissue LA has increased by 136% over the last half century and that this increase is highly correlated with an increase in dietary LA intake over the same period of time.

Linoleic acid and breast cancer risk: a meta-analysis.

Prior studies on linoleic acid, the predominant n-6 fatty acid, and breast cancer risk have generated inconsistent results. We performed a meta-analysis to summarize the evidence regarding the relationship of dietary and serum linoleic acid with breast cancer risk. Pertinent studies were identified by a search of PubMed and EMBASE. The fixed- or random-effect pooled measure was selected based on between-study heterogeneity. Eight prospective cohort studies and four prospective nested case-control studies, involving 10 410 breast cancer events from 358 955 adult females across different countries, were included in present study. Compared with the lowest level of linoleic acid, the pooled relative risk (RR; 95 % CI) of breast cancer was 0·98 (0·93, 1·04) for the highest level of linoleic acid. The pooled RR (95 % CI) for dietary and serum linoleic acid were 0·99 (0·92, 1·06) and 0·98 (0·88, 1·08), respectively. The RR (95 % CI) of breast cancer was 0·97 (0·91, 1·04), 0·95 (0·85, 1·07), 0·96 (0·86, 1·07), 0·98 (0·87, 1·10) and 0·99 (0·85, 1·14) for linoleic acid intake of 5, 10, 15, 20 and 25 g/d, respectively. The risk of breast cancer decreased by 1 % (RR=0·99; 95 % CI 0·93, 1·05) for every 10 g/d increment in linoleic acid intake. This meta-analysis indicated that both dietary linoleic acid intake and serum linoleic acid level were associated with decreased risk of breast cancer, although none of the associations were statistically significant. Further investigations are warranted.

Relationship between polyunsaturated fatty acid levels in maternal diets and human milk in the first month post-partum.

The present study evaluated the relationship between dietary fatty acid (FA) intakes and human milk FA levels. Healthy lactating women (n = 514) from Northern China participated in the study. Dietary intake was assessed with a 24-h dietary recall questionnaire and evaluated using golden key maternal nutrition software (Wincome, Shanghai, China) and China Food Composition 2009. Human milk FA composition was determined by gas chromatography. The maternal daily median intakes of linoleic acid (LA), α-linolenic acid (ALA) and arachidonic acid (AA) were 19.93 g, 3.08 g and 16.33 mg, respectively. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes were below the recommended levels. FA levels in 100 g of human milk were 0.363 g LA, 0.038 g γ-linolenic acid (GLA), 0.052 g dihomo γ-linolenic acid (DGLA), 0.144 g ALA, 0.079 g AA, 0.007 g EPA, 0.018 g docosatetraenoic acid (DTA) and 0.048 g DHA. Multiple linear regression analysis revealed that human milk DGLA levels were negatively correlated with dietary LA intake (β = -0.223, P = 0.030), and human milk GLA and DTA levels were negatively correlated with dietary ALA intake (β = -2.189, P = 0.031; β = -2.252, P = 0.027) after adjusting for possible confounding factors. The results of the present study suggest the presence of competitive interactions between n-3 fatty acids (ALA) and n-6 fatty acids (GLA and DTA).

Excessive dietary linoleic acid induces proinflammatory markers in rats

Following the historical dietary recommendations, the substitution of polyunsaturated fatty acids (PUFAs) for saturated fatty acids (SFAs) resulted in a dramatic increase of linoleic acid (LA) in the Western diet. While proatherogenic properties of SFAs have been described, the involvement of LA on the inflammatory process remains controversial. Herein, we evaluated the effects of an excessive LA intake on the cytokine-induced expression of endothelial adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1), through the nuclear factor (NF)-κB pathway, in comparison with a control diet and regarding a “positive” SFA diet. Wistar rats were fed experimental diets — a control diet or diets enriched with LA or SFA — for 11 weeks. Plasma lipid parameters and proinflammatory cytokine production such as interleukin-1β and tumor necrosis factor (TNF)-α were analyzed. Expression of endothelial adhesion molecules and NF-κB was determined by immunohistochemical analysis. No difference was observed in body weight. The enriched diets did not affect triglyceride and total cholesterol levels in plasma. Our results demonstrated that excessive dietary LA intake increased TNF-α levels (P<.05) in plasma. Rats fed the LA-enriched diet showed a significantly higher expression of VCAM-1, ICAM-1 and NF-κB in aortas. In addition, our results demonstrated that an excess of LA is more efficient to activate endothelial molecular process than an excess of SFA. The present study provides further support for the proinflammatory properties of LA and suggests an LA-derivatives pathway involved in the inflammatory process.

Plasma linoleic acid partially mediates the association of bipolar disorder on self-reported mental health scales

We have shown that bipolar individuals have reduced quality diets, including lower intake of polyunsaturated fatty acids (PUFA). We have also reported reduced plasma levels of the n-6 PUFA, linoleic acid (LA), and the n-3 PUFA, eicosapentaenoic acid (EPA) in bipolar subjects. In the current analysis we hypothesized that LA and EPA plasma levels would mediate lower self-reported mental health and life functioning scores in bipolar subjects. In a cross-sectional study, we collected a 7-day diet record in bipolar (n = 56) and control subjects (n = 46) followed by a fasted blood draw. We used structured equation modeling path analysis to test for mediating effects of dietary intake and plasma levels of LA and EPA on self-reported mental health questionnaire scores, including the Life Functioning Questionnaire (LFQ), the Patient Health Questionnaire (PHQ9), and the Short Form Health Survey (SF12), extracting the mental health component summary score (SF12-MH). We adjusted for age, gender, psychiatric medication use, body mass index (BMI), and total caloric intake as covariates with bipolar disorder as the primary predictor. We found a significant path association from bipolar disorder to lower plasma LA levels (p = 0.03) and significant paths from plasma LA to PHQ9 (p = 0.05), LFQ (p = 0.01) and SF12-MH (p = 0.05) scores, such that lower plasma LA predicted worse outcomes. We found no significant paths from plasma EPA levels to any of the outcome measures. These findings suggest that plasma LA levels partially mediate the effect of bipolar disorder on self-reported measures of mental health and life functioning.

Dietary Linoleic and α-Linolenic Acids Affect Anxiety-Related Responses and Exploratory Activity in Growing Pigs1–3

Growing evidence suggests that the dietary ratio of linoleic acid (LA) to α-linolenic acid (ALA), the precursors of arachidonic acid (AA) and docosahexaenoic acid (DHA), respectively, may affect behavior in mammals. This study aimed at evaluating the impact of dietary LA and ALA intake on behaviors of growing pigs, a pertinent model for human nutrition. At 7 wk of age, 32 pigs were allocated to 4 dietary treatments varying in daily intake of LA (1.3 and 2.6 g · kg body weight(-0.75) · d(-1) for low- and high-LA groups, respectively) and ALA (0.15 and 1.5 g · kg body weight(-0.75) · d(-1) for low- and high-ALA groups, respectively) for 4 wk. Between days 12 and 18, general behavior in the home pen was observed and pigs were subjected to an open field and novel object test. At 11 wk of age, brain fatty acid composition was analyzed. Compared with high LA intake, low LA intake increased the time spent on exploration, particularly nosing in the home pen (P < 0.05) and the open field (P < 0.05), and tended to reduce the time spent lying with eyes open in the home pen (P = 0.09). Time spent lying with eyes open also tended to be affected by the interaction between LA and ALA (P = 0.08). A high-LA/high-ALA intake (ratio of 2; P < 0.05) and a low-LA/high-ALA intake (ratio of 1; P = 0.06) decreased the latency to approach the novel object compared with a low-LA/low-ALA intake (ratio of 9). DHA in the frontal cortex was positively correlated with exploratory behaviors in the home pen (rs = 0.56, P < 0.01), whereas AA was negatively correlated with time spent lying with eyes closed (rs = -0.48, P < 0.01). Low LA intake and a low dietary LA:ALA ratio increased exploration and decreased anxiety-related behaviors in pigs. It is suggested that changes in brain DHA and AA induced by dietary LA and ALA intake mediate these behavioral changes.

Dietary linoleic acid and risk of coronary heart disease: a systematic review and meta-analysis of prospective cohort studies.

Previous studies on intake of linoleic acid (LA), the predominant n-6 fatty acid, and coronary heart disease (CHD) risk have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of dietary LA intake and CHD risk. We searched MEDLINE and EMBASE databases through June 2013 for prospective cohort studies that reported the association between dietary LA and CHD events. In addition, we used unpublished data from cohort studies in a previous pooling project. We pooled the multivariate-adjusted relative risk (RR) to compare the highest with the lowest categories of LA intake using fixed-effect meta-analysis. We identified 13 published and unpublished cohort studies with a total of 310 602 individuals and 12 479 total CHD events, including 5882 CHD deaths. When the highest category was compared with the lowest category, dietary LA was associated with a 15% lower risk of CHD events (pooled RR, 0.85; 95% confidence intervals, 0.78-0.92; I(2)=35.5%) and a 21% lower risk of CHD deaths (pooled RR, 0.79; 95% confidence intervals, 0.71-0.89; I(2)=0.0%). A 5% of energy increment in LA intake replacing energy from saturated fat intake was associated with a 9% lower risk of CHD events (RR, 0.91; 95% confidence intervals, 0.87-0.96) and a 13% lower risk of CHD deaths (RR, 0.87; 95% confidence intervals, 0.82-0.94). In prospective observational studies, dietary LA intake is inversely associated with CHD risk in a dose-response manner. These data provide support for current recommendations to replace saturated fat with polyunsaturated fat for primary prevention of CHD.

A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans

This study aimed to determine the effect of reducing the dietary linoleic acid (LA) intake from ~5% to <2.5% energy (%E) on n-3 long chain PUFA (LCPUFA) status in humans. Thirty-six participants followed a <2.5%E LA diet for 4 weeks. Nutrient intakes were estimated from diet diaries and blood samples were collected for assessment of fatty acid composition in plasma and erythrocyte phospholipids. LA intakes were reduced from 4.6%E to 2%E during the low LA intervention (P<0.001) while n-3 LCPUFA intakes were unchanged. LA and total n-6 PUFA content of plasma and erythrocyte phospholipids were significantly reduced after the low LA diet phase (P<0.001). The n-3 LCPUFA content of plasma phospholipids was significantly increased after the low LA diet compared to baseline (6.22% vs. 5.53%, P<0.001). These data demonstrate that reducing LA intake for 4 weeks increases n-3 LCPUFA status in humans in the absence of increased n-3 LCPUFA intake.