Dietary Intake Of Linoleic Acid Research Articles

Associations of dietary linoleic acid and alpha linolenic acid intake with cardiovascular, cancer and all-cause mortalities in patients with diabetes: NHANES 1999-2008.

To investigate the association between the dietary intake of linoleic acid (LA) and alpha linolenic acid (ALA) with mortality outcomes in patients with diabetes. 3,112 U.S. adults aged≥20 years. Basic information was collected at baseline of the National Health and Nutrition Examination Survey (NHANES). Serum CRP (mg/dL), total protein (g/L), waist circumference (cm), fasting blood glucose (mmol/L), white blood cell count, serum LDL-C, and serum HDL-C were also measured. Daily diets were also recorded using a 24-hour dietary review to produce the individuals' intake of LA and ALA. The association between tertiles of LA and ALA intake with mortality was analyzed by weighted Cox models adjusted for the main confounders. The study included 3,112 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2008. Death outcomes were ascertained by linkage to the database records through 31 December 2015. Subjects with a high intake of LA (T3) had 17% [hazard ratio (HR) 0.83, 95% CI 0.70 to 0.99) and 48% (HR=0.52, 0.35 to 0.80)] reductions in all-cause mortality and cardiovascular mortality, respectively, compared with subjects with lowest intake (T1). Similar results were observed for ALA, HR of cardiovascular mortality was 0.55 (0.38 to 0.81) and for all-cause mortality was 0.85 (0.69 to 1.04) comparing the highest to lowest intake tertiles. Higher intakes of LA and ALA were inversely associated with CVD and all-cause deaths in patients with diabetes. Proper dietary intakes of LA and ALA could contribute to the cardiovascular health and the long-term survival of patients with diabetes.

Replacement of saturated fatty acids with linoleic acid in western diet attenuates atherosclerosis in a mouse model with inducible ablation of hepatic LDL receptor

Dietary saturate fatty acids (SFAs) have been consistently linked to atherosclerosis and obesity, both of which are characterized by chronic inflammation and impaired lipid metabolism. In comparison, the effects of linoleic acid (LA), the predominant polyunsaturated fatty acid in the Western diet, seem to diverge. Data from human studies suggest a positive association between high dietary intake of LA and the improvement of cardiovascular risk. However, excessive LA intake has been implicated in the development of obesity. Concerns have also been raised on the potential pro-inflammatory properties of LA metabolites. Herein, by utilizing a mouse model with liver-specific Ldlr knockdown, we directly determined the effects of replacing SFAs with LA in a Western diet on the development of obesity and atherosclerosis. Specifically, mice treated with a Ldlr ASO were placed on a Western diet containing either SFA-rich butter (WD-B) or LA-rich corn oil (WD-CO) for 12 weeks. Despite of showing no changes in body weight gain or adiposity, mice on WD-CO exhibited significantly less atherosclerotic lesions compared to those on WD-B diet. Reduced lesion formation in the WD-CO-fed mice corresponded with a reduction of plasma triglyceride and cholesterol content, especially in VLDL and LDL, and ApoB protein levels. Although it increased expression of proinflammatory cytokines TNF-α and IL-6 in the liver, WD-CO did not appear to affect hepatic injury or damage when compared to WD-B. Collectively, our results indicate that replacing SFAs with LA in a Western diet could reduce the development of atherosclerosis independently of obesity.

Dietary linoleic acid intake in relation to breast cancer: A case-control study.

The present study aimed to investigate the association between dietary linoleic acid (LA) intake and breast cancer in women. In this population-based case-control study, we enrolled 350 pathologically confirmed breast cancer cases and 700 controls which were matched with cases in terms of age and socioeconomic status. Dietary intakes were assessed using a 106-item Willett-format semi-quantitative dish-based food frequency questionnaire (DS-FFQ). Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated. A significant inverse association was found between LA intake and odds of breast cancer (OR: 0.41, 95% CI: 0.30-0.56). After adjusting for potential confounders, women in the highest tertile of dietary LA intake were 48% less likely to have breast cancer compared with those in the lowest tertile (OR: 0.52, 95% CI: 0.28-0.95). Such a significant inverse association was also seen among normal-weight women (OR: 0.29, 95% CI: 0.14-0.63), and premenopausal women (OR: 0.15, 95% CI: 0.02-0.95). The findings of current study provide evidence for a protective role of LA against breast cancer particularly among normal-weight and premenopausal women. Prospective studies are needed to confirm this association.

Differential Association of Dietary Linoleic Acid and Alpha-linolenic Acid with Adipose Tissue in a Sample of Iranian Adults; A Cohort-based Cross-sectional Study.

Overweight and obesity are the most critical risk factors for chronic diseases. The quality of dietary fatty acids as one of the factors affecting fat accumulation has received little attention. This study investigates the association between dietary linoleic acid (LA) and alpha-linolenic acid (ALA) with body fat indices in a sample of healthy Iranian adults. In this cohort-based cross-sectional study, 3,195 individuals aged 20 to 60 who participated in the Shiraz University of Medical Science Employees Health Cohort study were included. Dietary intake was assessed using a validated 118-item Food Frequency Questionnaire (FFQ), and body composition was assessed by the bioelectrical impedance analysis method. Multiple linear regression adjusted for relevant confounders was used to determine the associations. Mean dietary intake of LA was 14.20 ± 7.01 mg/day for men and 13.90 ± 6.71 mg/day for women. Additionally, the daily intake of ALA was 0.18 ± 0.18 mg/day in men and 0.17 ± 0.19 mg/day in women. Dietary intake of ALA for men had an inversely significant association with body fat mass (BFM) (β: -0.585, 95% CI: -1.137, -0.032, P=0.038), percentage of body fat (PBF) (β: -0.537, 95% CI: -0.945, -0.129, P=0.010), Visceral Fat Area (VFA) (β: -2.998, 95% CI: -5.695, -0.302, P=0.029), and Waist to Hip Ratio (WHR) (β: -0.689, 95% CI: -1.339, -0.040, P=0.038). Higher dietary ALA intake was associated with lower BFM, BFP, VAF, and WHR in men. The present study confirms that ALA intake should be considered a preventive treatment to improve body composition. However, further research is recommended in this regard.

Linoleic Acid: A Narrative Review of the Effects of Increased Intake in the Standard American Diet and Associations with Chronic Disease.

The intake of linoleic acid (LA) has increased dramatically in the standard American diet. LA is generally promoted as supporting human health, but there exists controversy regarding whether the amount of LA currently consumed in the standard American diet supports human health. The goal of this narrative review is to explore the mechanisms that underlie the hypothesis that excessive LA intake may harm human health. While LA is considered to be an essential fatty acid and support health when consumed in modest amounts, an excessive intake of LA leads to the formation of oxidized linoleic acid metabolites (OXLAMs), impairments in mitochondrial function through suboptimal cardiolipin composition, and likely contributes to many chronic diseases that became an epidemic in the 20th century, and whose prevalence continues to increase. The standard American diet comprises 14 to 25 times more omega-6 fatty acids than omega-3 fatty acids, with the majority of omega-6 intake coming from LA. As LA consumption increases, the potential for OXLAM formation also increases. OXLAMs have been associated with various illnesses, including cardiovascular disease, cancer, and Alzheimer's disease, among others. Lowering dietary LA intake can help reduce the production and accumulation of OXLAMs implicated in chronic diseases. While there are other problematic components in the standard American diet, the half-life of LA is approximately two years, which means the damage can be far more persistent than other dietary factors, and the impact of reducing excessive LA intake takes time. Therefore, additional research-evaluating approaches to reduce OXLAM formation and cardiolipin derangements following LA consumption are warranted.

Effects of Dietary Linoleic Acid on Blood Lipid Profiles: A Systematic Review and Meta-Analysis of 40 Randomized Controlled Trials.

Th aim of this meta-analysis was to elucidate whether dietary linoleic acid (LA) supplementation affected blood lipid profiles, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), compared with other fatty acids. Embase, PubMed, Web of Science and the Cochrane Library databases, updated to December 2022, were searched. The present study employed weighted mean difference (WMD) and a 95% confidence interval (CI) to examine the efficacy of the intervention. Out of the 3700 studies identified, a total of 40 randomized controlled trials (RCTs), comprising 2175 participants, met the eligibility criteria. Compared with the control group, the dietary intake of LA significantly decreased the concentrations of LDL-C (WMD: -3.26 mg/dL, 95% CI: -5.78, -0.74, I2 = 68.8%, p = 0.01), and HDL-C (WMD: -0.64 mg/dL, 95% CI: -1.23, -0.06, I2 = 30.3%, p = 0.03). There was no significant change in the TG and TC concentrations. Subgroup analysis showed that the LA intake was significantly reduced in blood lipid profiles compared with saturated fatty acids. The effect of LA on lipids was not found to be dependent on the timing of supplementation. LA supplementation in an excess of 20 g/d could be an effective dose for lowering lipid profiles. The research results provide further evidence that LA intake may play a role in reducing LDL-C and HDL-C, but not TG and TC.

Excessive dietary linoleic acid promotes plasma accumulation of pronociceptive fatty acyl lipid mediators

Various fatty acyl lipid mediators are derived from dietary polyunsaturated fatty acids (PUFAs) and modulate nociception. The modern diet is rich in linoleic acid, which is associated with nociceptive hypersensitivities and may present a risk factor for developing pain conditions. Although recommendations about fatty acid intake exist for some diseases (e.g. cardiovascular disease), the role of dietary fatty acids in promoting pain disorders is not completely understood. To determine how dietary linoleic acid content influences the accumulation of pro- and anti-nociceptive fatty acyl lipid mediators, we created novel rodent diets using custom triglyceride blends rich in either linoleic acid or oleic acid. We quantified the fatty acyl lipidome in plasma of male and female rats fed these custom diets from the time of weaning through nine weeks of age. Dietary fatty acid composition determined circulating plasma fatty acyl lipidome content. Exposure to a diet rich in linoleic acid was associated with accumulation of linoleic and arachidonic acid-derived pro-nociceptive lipid mediators and reduction of anti-nociceptive lipid mediators derived from the omega-3 PUFAs. Our findings provide mechanistic insights into exaggerated nociceptive hypersensitivity associated with excessive dietary linoleic acid intake and highlight potential biomarkers for pain risk stratification.

Association between dietary intake of fatty acids and colorectal cancer, a case-control study.

BackgroundThe association of dietary fat and colorectal cancer (CRC) was frequently reported. However, few studies assessed the effects of different types of dietary fats on CRC. This study aimed to investigate the association between intakes of different types of dietary fatty acids with colorectal cancer risk.MethodsThis case-control study was conducted on 480 participants including 160 CRC cases and 320 healthy controls in Firoozgar Hospital, Tehran, Iran. The intake of dietary fatty acids of the participants was assessed using a semi quantitative food frequency questionnaire (FFQ).ResultsThe mean intake of cholesterol (273.07 ± 53.63 vs. 254.17 ± 61.12, P = 0.001), polyunsaturated fatty acids (PUFA) (16.54 ± 4.20 vs. 15.41 ± 4.44, P = 0.012), and calorie (2,568.76 ± 404.48 vs. 2,493.38 ± 176.03, P = 0.006) was higher and the mean intake of oleic acid (5.59 ± 3.17 vs. 8.21 ± 5.46) and linoleic acid (6.03 ± 3.44 vs. 7.02 ± 4.08, P = 0.01) was lower in the case group compared to the control group. An inverse association was found between colorectal cancer (CRC) and dietary intake of oleic acid (OR: 0.85, CI 95% 0.80–0.90, P = 0.001), linoleic acid (OR: 0.85, CI 95% 0.78–0.93, P = 0.001), and α-linolenic acid (OR: 0.75, CI 95% 0.57–0.98, P = 0.04). The association remained significant after adjusting for age and sex, sleep, smoking, and alcohol consumption, and BMI.ConclusionsThe results of this study support a protective effect of oleic acid, linoleic acid, and α-linolenic acid against CRC. Further longitudinal studies are warranted to confirm these results.

Suppressive GLI2 fragment enhances liver metastasis in colorectal cancer.

Linoleic acid (LA) has been shown to cause inflammation and promote development of colorectal cancer (CRC). Moreover, many literatures show that LA is associated with cancer metastasis. Metastatic cancer cells have high stemness, suggesting that LA might affect the stemness of cancer cells. In this study, we examined the effect of LA on the hedgehog system, which affects cancer stemness. In CT26 cells, LA treatment induced the expression of sonic hedgehog (Shh); the signal transduction factor, and glioma-associated oncogene homolog (Gli) 2, whereas the expression of SRY-box transcription factor (Sox) 17 was suppressed. Furthermore, LA reduced GLI2 ubiquitination, resulting in an increase in the N-terminal fragment of GLI2, known as suppressive GLI2, produced by cleavage of GLI2. LA-induced cleaved GLI2 was also detected in Colo320 and HT29 human CRC cells. Knocking down Gli2 abrogated the LA-mediated suppression of Sox17 expression. These results suggest that LA promotes tumor cell stemness by increasing of suppressive GLI2 fragments via GLI2 modification. In mouse liver metastasis models, LA enhanced metastasis with production of the suppressive GLI2 fragments in CT26 and HT29 cells, whereas knockdown of GLI2 abrogated LA-induced metastatic activity. In human CRCs, the cases with liver metastasis showed the suppressive GLI2 fragments. This study provides mechanistic insights into LA-induced stemness in colon cancer cells. This finding suggests that dietary intake of LA might increase the stemness of cancer cells and enhance metastatic activity of the cancer.

Red blood cell fatty acids and age-related macular degeneration in postmenopausal women.

To evaluate the relationship between red blood cell (RBC) polyunsaturated fatty acid (PUFA) levels, and dietary PUFA and fish intake, with prevalent and incident age-related macular degeneration (AMD) in a US cohort of postmenopausal women. This analysis included 1456 postmenopausal women from the Women's Health Initiative (WHI) Clinical Trials. RBC PUFAs were measured from fasting serum samples collected at WHI baseline. Dietary PUFAs and fish intake were assessed via food frequency questionnaires at baseline. There were 240 women who had prevalent AMD and 138 who self-reported AMD development over 9.5years. Adjusted odds ratios and 95% confidence intervals were estimated for prevalent AMD by RBC PUFA levels, dietary PUFA intake, and frequency of fish consumption. Adjusted hazard ratios and 95% confidence intervals were estimated for incident AMD. A p-for-trend was estimated for continuous measures of dietary PUFA and fish intake. No significant association was found between prevalent or incident AMD and RBC docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), EPA, DHA, alpha-linolenic acid (ALA), linoleic acid (LA), or arachidonic acid (AA). A positive association was found between dietary intake of AA and odds of prevalent AMD (p-for-trend for continuous AA intake = 0.02) and between intake of LA/ALA and incident AMD (p-for-trend for continuous ratio of LA/ALA intake = 0.03). No statistically significant associations were found between AMD and dietary intake of PUFAs or fish. RBC PUFAs were not associated with AMD in this cohort. Overall, dietary analyses of PUFAs supported this, excepting dietary AA intake and intake of LA in proportion to ALA of which there were trends of increased risk.

Dietary Intake of Linoleic Acid, Its Concentrations, and the Risk of Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies.

Earlier evidence on the association between dietary polyunsaturated fatty acids and risk of diabetes has been conflicting. To quantitatively summarize previous studies on the association between dietary LA intake, its biomarkers, and the risk of type 2 diabetes mellitus (T2DM) in the general population. Our data sources included PubMed/MEDLINE, Scopus, and ISI Web of Science until 24 October 2020; reference lists of all related articles; and key journals. We included prospective cohort studies that examined the associations of linoleic acid (LA) with the risk of T2DM in adults. The inverse variance method was applied to calculate summary relative risk (RR) of LA intake and its biomarkers, and dose-response associations were modeled using restricted cubic splines. Twenty-three publications, covering a total of 31 prospective cohorts, were included; these studies included 297,685 participants (22,639 incident diabetes cases) with dietary intake assessment and 84,171 participants (18,458 incident diabetes cases) with biomarker measurements. High intake of LA was associated with a 6% lower risk of T2DM (summary relative risk [RR] 0.94, 95% CI 0.90, 0.99; I 2 = 48.5%). In the dose-response analysis, each 5% increment in energy from LA intake was associated with a 10% lower risk of T2DM. There was also evidence of a linear association between LA intake and diabetes, with the lowest risk at highest intakes. The summary RR for diabetes per SD increment in LA concentrations in adipose tissue/blood compartments was 0.85 (95% CI 0.80, 0.90; I2 = 66.2%). The certainty of the evidence was assessed as moderate. A limitation of our work was the observational design of studies included in the analyses. We found that a high intake of dietary LA and elevated concentrations of LA in the body were both significantly associated with a lower risk of T2DM. These findings support dietary recommendations to consume dietary LA.

Dietary Linoleic Acid: Will Modifying Dietary Fat Quality Reduce the Risk of Type 2 Diabetes?

Linoleic acid (LA) is the major polyunsaturated fatty acid (PUFA) in Western diets; e.g., it accounts for almost 90% of PUFA intake in the U.S. diet (1). Intake levels as a percentage of total energy have increased over time in the U.S. (2), with mean intake being right within the range recommended by the U.S. Institute of Medicine (5–10%) (3). Although the intake of PUFA has been part of dietary recommendations for cardiovascular risk prevention, usually in the context of reducing intake of saturated fatty acids (SFA) (4), the American Diabetes Association does not clearly emphasize LA as a component of diet quality for diabetes prevention (5). This might be due to the fact that there are no available data from trials designed to investigate diabetes incidence as an outcome. However, prospective observational studies have now accumulated a substantial amount of data on the relation between LA intake or status and diabetes incidence, which helpful for reevaluation of its role for diabetes prevention. In this issue of Diabetes Care , Mousavi et al. (6) summarize data from such prospective studies. They first systematically identified cohort studies on either dietary intake or tissue biomarkers of LA status and diabetes incidence. This led to nine cohorts on dietary intake, with a total of 22,639 cases of diabetes, and 27 cohorts on LA tissue biomarkers (including a total of 18,458 incident cases). The authors then performed meta-analyses of individual study findings. With regard to dietary intake of LA, results of the meta-analysis suggest an inverse association. This was evident in considering different categories of intake and also from a dose-response analysis, where each additional 5% of energy from LA was associated with a 10% lower risk …

Linoleic acid in adipose tissue and the risk of myocardial infarction: a case-cohort study.

We investigated risk of myocardial infarction (MI) associated with the content of linoleic acid (LA) in adipose tissue, a biomarker of long-term dietary intake of LA and a marker of endogenous LA exposure. Between 1993 and 1997, 57,053 middle-aged subjects were included in the Danish Diet, Cancer and Health cohort. We performed a case-cohort study that included a random sample of the full cohort (n = 3167) and all incident MI cases appearing during 16years of follow-up (n = 2819). Information on incident MI cases was obtained by linkage with Danish nationwide registries. Adipose tissue biopsies were taken from the buttocks of the participants, and their fatty acid composition was determined using gas chromatography. HRs (hazard ratios) with 95% confidence intervals (CIs) were used to describe the associations between content of LA in adipose tissue and the risk of MI. HRs were calculated using weighted Cox proportional hazards regression with robust variance. After adjustment for established risk factors of MI, adipose tissue content of LA was not associated with the risk of MI in men and women combined (quintiles 5 versus 1, HR, 1.03 (95% CI, 0.85-1.25), P-trend = 0.970) or in men and women separately (quintiles 5 versus 1, HR, 1.05 (95% CI, 0.83-1.33), P-trend = 0.871 and quintiles 5 versus 1, HR, 0.99 (95% CI 0.72-1.37), P-trend = 0.928, respectively). Investigating the association between LA and MI with a shorter, 5- or 10-year duration of follow-up provided similar results. Content of LA in adipose tissue was not associated with the risk of MI.

Different Ratios of Corn and Coconut Oil Blends in High‐Fat Diets Influence Fat Deposition without Altering Metabolic Biomarkers in Male Rats

AbstractThe effects of high‐fat diets with the recommended dietary linoleic acid (LA) intake levels on health outcomes have not been studied extensively. This study investigated the effects of high‐fat diets containing different weight ratios of coconut and corn oil with LA levels of <1.00% of energy (very low LA), 2.80% of energy (low LA), 5.80% of energy (moderate LA), and 9.70% of energy (high LA) on fat deposition and selected metabolic biomarkers of male Sprague‐Dawley rats. Their initial and terminal body weights are recorded. Blood, adipose tissue, and liver samples are obtained for analysis after an 8‐week feeding intervention. Compared with the very low‐LA diet, the high‐LA diet resulted in higher body weight gain and epididymal fat deposition. No significant differences are observed in liver‐to‐body weight ratio, blood glucose, visfatin, and leptin levels between the test diets. Serum tumor necrosis factor‐alpha (TNF‐α), insulin, and C‐peptide levels do not significantly increase with the increase in dietary LA levels. High‐LA diet results in higher LA levels in the liver and adipose tissue. It is concluded that a high‐fat diet containing high LA levels induced body weight gain and epididymal fat deposition in rats but has no effect on selected metabolic biomarkers.Practical applications: Linoleic acid (LA) (C18:2) plays an important role as one of the nutritional elements to meet the daily essential fatty acid requirements. However, a full understanding is perplexed by the various ways that LA can be included in the diet when there is a recommendation to substitute saturated fatty acid (SFA), trans‐ or n‐3 fatty acids intake. The data provide additional findings on the effects of excessive dietary intake of LA (C18:2) on fat deposition when different levels of SFAs are replaced.

Maternal High Linoleic Acid Alters Placental Fatty Acid Composition.

Fetal development is modulated by maternal nutrition during pregnancy. The dietary intake of linoleic acid (LA), an essential dietary n-6 polyunsaturated fatty acid (PUFA), has increased. We previously published that increased LA consumption during pregnancy does not alter offspring or placental weight but fetal plasma fatty acid composition; the developing fetus obtains their required PUFA from the maternal circulation. However, it is unknown if increased maternal linoleic acid alters placental fatty acid storage, metabolism, transport, and general placental function. Female Wistar-Kyoto rats were fed either a low LA diet (LLA; 1.44% of energy from LA) or high LA diet (HLA; 6.21% of energy from LA) for 10 weeks before pregnancy and during gestation. Rats were sacrificed at embryonic day 20 (E20, term = 22 days) and placentae collected. The labyrinth of placentae from one male and one female fetus from each litter were analyzed. High maternal LA consumption increased placental total n-6 and LA concentrations, and decreased total n-3 PUFA, alpha-linolenic acid (ALA), and docosahexaenoic acid (DHA). Fatty acid desaturase 1 (Fads1), angiopoietin-like 4 (Angptl4), and diacylglycerol lipase beta (Daglb) mRNA were downregulated in placentae from offspring from HLA dams. Maternal high LA downregulated the fatty acid transport protein 4 (Fatp4) and glucose transporter 1 (Slc2a1) mRNA in placentae. IL-7 and IL-10 protein were decreased in placentae from offspring from HLA dams. In conclusion, a high maternal LA diet alters the placental fatty acid composition, inflammatory proteins, and expressions of nutrient transporters, which may program deleterious outcomes in offspring.

Dietary intake and biomarkers of linoleic acid and mortality: systematic review and meta-analysis of prospective cohort studies

Current evidence on associations between intakes of linoleic acid (LA), the predominant n-6 (ω-6) fatty acid, and mortality is inconsistent and has not been summarized by a systematic review and meta-analysis. The aim was to perform a systematic review and meta-analysis of prospective cohort studies to examine associations between LA intake and mortality. We conducted a comprehensive search of MEDLINE and EMBASE databases through 31 July 2019 for prospective cohort studies reporting associations of LA (assessed by dietary surveys and/or LA concentrations in adipose tissue or blood compartments) with mortality from all causes, cardiovascular disease (CVD), and cancer. Multivariable-adjusted RRs were pooled using random-effects meta-analysis. Thirty-eight studies reporting 44 prospective cohorts were identified; these included 811,069 participants with dietary intake assessment (170,076 all-cause, 50,786 CVD, and 59,684 cancer deaths) and 65,411 participants with biomarker measurements (9758 all-cause, 6492 CVD, and 1719 cancer deaths). Pooled RRs comparing extreme categories of dietary LA intake (high vs low) were 0.87 (95% CI: 0.81, 0.94; I2=67.9%) for total mortality, 0.87 (95% CI: 0.82, 0.92; I2=3.7%) for CVD mortality, and 0.89 (95% CI: 0.85, 0.93; I2=0%) for cancer mortality. Pooled RRs for each SD increment in LA concentrations in adipose tissue/blood compartments were 0.91 (95% CI: 0.87, 0.95; I2=64.1%) for total mortality, 0.89 (95% CI: 0.85, 0.94; I2=28.9%) for CVD mortality, and 0.91 (95% CI: 0.84, 0.98; I2=26.3%) for cancer mortality. Meta-regressions suggested baseline age and dietary assessment methods as potential sources of heterogeneity for the association between LA and total mortality. In prospective cohort studies, higher LA intake, assessed by dietary surveys or biomarkers, was associated with a modestly lower risk of mortality from all causes, CVD, and cancer. These data support the potential long-term benefits of PUFA intake in lowering the risk of CVD and premature death.

Effects of Linoleic Acid-Rich Diet on Plasma Profiles of Eicosanoids and Development of Colitis in Il-10-/- Mice.

Dietary intake of linoleic acid (LA, 18:2ω-6) has risen dramatically in recent decades. Previous studies have suggested a high intake of LA could increase tissue concentrations of proinflammatory and protumorigenic ω-6-series eicosanoid metabolites, increasing risks of inflammation and associated diseases. However, the effects of a LA-rich diet on in vivo profiles of eicosanoids and development of inflammatory diseases are understudied. Here, we treated spontaneous colitis-prone (Il-10-/-) mice with a control diet (∼3 Cal% LA) or a LA-rich diet (∼9 Cal% LA) for 18 weeks and analyzed the effects of the LA-rich diet on profiles of eicosanoids and development of colitis. We found that treatment with the LA-rich diet increased the tissue level of LA: the liver levels of LA were 5.8 ± 0.6% in the control diet-treated mice versus 11.7 ± 0.7% in the LA-rich diet-treated mice (P < 0.01). The plasma concentrations of a series of LA-derived metabolites, including 9-hydroxyoctadecadienoic acid (HODE), 9,10-dihydroxyoctadecenoic acid (DiHOME), 12,13-DiHOME, and 13-HODE were significantly increased by treatment with the LA-rich diet (P < 0.05). However, the LA-rich diet had little effect on the severity of colitis in the treated Il-10-/- mice. These results suggest a limited role of increased consumption of dietary LA on promoting colitis in the Il-10-/- model.

Variability in Salivary Cortisol is Associated with Body Mass Index and Diet Quality

Abstract Objectives Stress can negatively impact lifestyle practices and metabolic health, thereby increasing an individual's risk for chronic disease. We investigated whether variability in salivary cortisol levels is associated with body composition, blood pressure, and diet quality. Methods In this ongoing study, adult men and women (18–70y, n = 17) participated in a fasted baseline health assessment to measure body composition and resting blood pressure. Dietary intake was assessed over a 5-day period, where saliva samples were collected in the morning, afternoon, and evening to measure cortisol levels. Degree of cortisol variability over the 5-day period was calculated as: the highest recorded cortisol measurement - the lowest recorded cortisol measurement, which was used to classify subjects into groups of high (n = 9) and low (n = 8) cortisol variability. Results Subjects with greater variability in salivary cortisol had higher cortisol levels on average, in addition to greater concentrations and variability in cortisol levels in the morning. High variability in cortisol levels was additionally associated with a higher body mass index and metabolic age, but was not associated with fat or fat-free mass, waist circumference, or blood pressure. Subjects with lower variability in salivary cortisol levels reported having a greater dietary intake of linoleic acid and manganese, as well as a trend toward greater intake of vitamin D. Greater variability in salivary cortisol levels positively correlated with the % of dietary calories coming from fat, total fructose, serine, fried potatoes, dairy-based desserts, sweetened coffee, and beer. Conclusions Our preliminary findings demonstrate that high variability in salivary cortisol is associated with elevated morning stress hormone levels, body mass index, and a less favorable dietary pattern. Funding Sources This study was funded by the Fairfield University College of Arts and Sciences and a Vincent Rosivach Collaborative Research Grant.

Role of a Maternal Diet High in Linoleic Acid on the Plasma Fatty Acid Composition in Rat Offspring

Linoleic acid (LA) is a major omega‐6 polyunsaturated fatty acid (PUFA) which is essential in our diet. LA is an important fatty acid for fetal growth and development and is transported from mother to fetus through the placenta. Dietary intake of LA has increased significantly in western societies primarily due to increased consumption of vegetable oils. Conversely, the consumption of alpha‐linolenic acid (ALA), an omega‐3 PUFA, has remained similar or decreased due to limited consumption of fish. Metabolites of omega‐3 PUFAs such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) have critical roles in fetal neural development and may influence brain function in later in life. The aim of this study is to investigate the effect of a maternal diet high in LA on offspring fatty acid composition at 40 days of age (adolescence). Female rats were fed with either low LA diet (LLA; 1.44% of energy from LA) or high LA (HLA; 6.21% of energy from LA) with matched ALA (0.3% of energy) for 10 weeks before pregnancy and during gestation. The pups were weaned at postnatal day 25 (PN25) and fed with either LLA or HLA diet (Four groups ‐ LL, LH, HL, HH; first letter denotes maternal diet and second letter denotes post‐weaning diet). The offspring were sacrificed at postnatal day 40 and biological samples were collected and stored at −80°C. The concentration of fatty acids in plasma was quantified using gas chromatography. Total omega‐6 fatty acid (FA) and LA levels in plasma were significantly elevated in the offspring fed with HLA diet at weaning and offspring from dams fed with HLA (LH, HL, HH) compared to offspring from LLA dams fed with LLA at weaning (LL) both in male and female offspring. Total omega‐3 FA was significantly decreased in offspring from HLA dams fed with HLA diet (HH) at weaning in comparison to offspring from LLA dams fed with LLA at weaning (LL). The concentration of ALA was significantly decreased in male offspring from HLA dams fed with HLA diet (HH) compared to HL offspring; however, there was no difference in female offspring. In addition, the plasma level of EPA was significantly decreased in male offspring fed with HLA diet at weaning (LH and HH) compared with LL offspring; however, there was no difference in female offspring. Moreover, DHA, an important omega‐3 FA for brain development, was significantly decreased in HH offspring compared to LL offspring. Hence, the findings from the current study suggest that elevated LA in both maternal diet and weaning diet influence the plasma fatty acid composition in adolescent offspring in a rat model.Support or Funding InformationThis work was supported by the Allen Foundation (D.H.H., A.J.M.), and through the Australian Government's Collaborative Research Networks (CRN) programme (A.J.M.). Scholarship funding is provided by Griffith University International Postgraduate Research Scholarship (GUIPRS; N.S.), Griffith University Postgraduate Research Scholarship (GUPRS, N.S.) and Griffith Health Top Up Scholarship (N.S.). B.S.M. is supported by a National Health and Medical Research Council of Australia Career Development Award (Level 2) (APP1083009).

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.