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The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) underscores the need for better understanding of its complex pathogenesis. Lipid accumulation in hepatocytes is among principal mechanisms contributing to MASLD development. While routine lipid parameters are well studied, the profile of circulating fatty acids in MASLD patients remains less explored. This study aimed to assess relative proportions of individual fatty acids in plasma of MASLD patients and to explore their associations with other biochemical markers of MASLD. Ninety-one patients and 48 healthy individuals were enrolled. The relative proportions of fatty acids in plasma were determined using gas chromatography with FID detection. Proportions of total n-6 polyunsaturated fatty acids (PUFAs) and linoleic acid (LA) in plasma were lower in MASLD patients (p = 0.001 and p = 0.004, respectively), with no differences observed in n-3 PUFAs. Total plasma n-6 PUFAs correlated negatively with body mass index, hepatic steatosis indices, triglyceride concentration and coronary risk index. Decreased prevalence of n-6 PUFAs in plasma was independently associated with higher odds of MASLD (OR = 0.769; CI: 0.611–0.968; p = 0.025). Our findings indicate an altered circulatory fatty acid distribution in MASLD, characterized by a reduced amount of n-6 PUFAs, particularly LA, which may have significant implications for the prevention and treatment of MASLD. [ABSTRACT FROM AUTHOR]

The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) underscores the need for better understanding of its complex pathogenesis. Lipid accumulation in hepatocytes is among principal mechanisms contributing to MASLD development. While routine lipid parameters are well studied, the profile of circulating fatty acids in MASLD patients remains less explored. This study aimed to assess relative proportions of individual fatty acids in plasma of MASLD patients and to explore their associations with other biochemical markers of MASLD. Ninety-one patients and 48 healthy individuals were enrolled. The relative proportions of fatty acids in plasma were determined using gas chromatography with FID detection. Proportions of total n-6 polyunsaturated fatty acids (PUFAs) and linoleic acid (LA) in plasma were lower in MASLD patients (p = 0.001 and p = 0.004, respectively), with no differences observed in n-3 PUFAs. Total plasma n-6 PUFAs correlated negatively with body mass index, hepatic steatosis indices, triglyceride concentration and coronary risk index. Decreased prevalence of n-6 PUFAs in plasma was independently associated with higher odds of MASLD (OR = 0.769; CI: 0.611–0.968; p = 0.025). Our findings indicate an altered circulatory fatty acid distribution in MASLD, characterized by a reduced amount of n-6 PUFAs, particularly LA, which may have significant implications for the prevention and treatment of MASLD.

Triacylglycerols (TAG) are the primary sources of preformed fatty acids (FA) for lipid synthesis in the mammary gland. However, polyunsaturated FA escaping ruminal biohydrogenation are selectively incorporated into cholesterol esters (CE) and phospholipids (PL). The aim of the current experiment was to study the effects of abomasal infusion of increasing amount of linseed oil (L-oil) on plasma distribution of α-linolenic acid (α-LA) and its transfer efficiency into milk fat. Five rumen-fistulated Holstein cows were randomly distributed in a 5 × 5 Latin square design. Abomasal infusion of L-oil (55.9% α-LA) was performed at the rate of 0, 75, 150, 300, and 600 ml/d. Concentrations of α-LA increased quadratically in TAG, PL, and CE; a less steep slope was observed with an inflexion at an infusion rate of 300 ml L-oil per day. The increase in plasma concentration of α-LA was of a lower magnitude in CE as compared with the other two fractions, resulting in a quadratic decrease in relative proportion of this FA circulating as CE. The transfer efficiency into milk fat increased from 0 to 150 ml L-oil infused, and a plateau was maintained thereafter with greater levels of infusion (quadratic response). This pattern resembles the quadratic response of the relative proportion of α-LA circulating as TAG, and the relative concentration of this FA in TAG. Increasing the postruminal supply of α-LA partly overcame the segregation mechanism of absorbed polyunsaturated FA in different plasma lipid classes. Proportionately more α-LA was then esterified as TAG, at the expense of CE, increasing its efficiency of transfer into milk fat. This mechanism appears to be surpassed in its turn when L-oil infusion was increased over 150 ml/d. Nevertheless, the yield of α-LA in milk fat continued to increase, but at a slower rate at the highest levels of infusion. [ABSTRACT FROM AUTHOR]

Teng Zhang,1,2,&ast; Juan Huang,1,3,&ast; Yanru Li,1,&ast; Dubo Zhong,4 Songmei Wang,1 Fang Xu,1 Xuehui Zhang,1 Yuemei Feng,1 Jianzhong Yin1,2 1School of Public Health, Kunming Medical University, Kunming, People’s Republic of China; 2Baoshan College of Traditional Chinese Medicine, Baoshan, People’s Republic of China; 3Ultrasonography Department, First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4Yunnan Yunce Quality Inspection Limited Company, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianzhong Yin, Baoshan College of Traditional Chinese Medicine, Longyang District, Baoshan, Yunnan Province, 678000, People’s Republic of China, Tel +86 13987645337, Email yinjianzhong2005@sina.com Yuemei Feng, School of Public Health, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, People’s Republic of China, Tel +86 13678754163, Email fengyuemei2013@163.comBackground: Dietary fatty acids (DFAs) and plasma fatty acids (PFAs) are linked to obesity. However, whether this association exists among ethnic minorities remains lacking. The present cross-sectional study was designed to investigate the correlation between DFAs, PFAs and obesity in four ethnic minority groups to Southwest China.Methods: A total of 166 obese people, and 166 normal-BMI subjects matched based on their age-, sex-, and ethnicity- were recruited from four different ethnic minority groups. DFAs were obtained through food frequency questionnaires. PFAs were assayed by GC/MS method. Binary and multiple regression analyses were performed to evaluate the correlation among DFAs, PFAs and obesity. Canonical correlation analysis (CCA) was conducted to assess the relationship between DFAs and PFAs.Results: FAs were found to be highest in the Naxi people and lowest in the Hani people. Multiple logistic regression analysis revealed that plasma C16:0 (OR = 1.310; 95% CI, 1.028– 1.669) in the Hani people; plasma C20:3 n-6 (OR = 6.250; 95% CI, 1.224– 31.927) and dietary C20:1 (OR = 9.231; 95% CI, 1.253– 68.016) in the Wa people; plasma C18:0 (OR = 0.788; 95% CI, 0.681– 0.912) in the Naxi people were seen to be independent predictive factors for obesity. CCA showed that DFAs were positively correlated with PFAs in the Naxi (r: 0.676; P < 0.05) and Bulang people (r: 0.897; P < 0.05), but there was no correlation in the Hani and Wa people.Conclusion: In this study, PFAs but not DFAs were independently associated with obesity, and different among the four ethnic minorities.Keywords: dietary fatty acids, plasma fatty acids, obesity, minorities, canonical correlation analysis

Abstract Background Despite the wide use of parenteral nutrition (PN) in neonatal intensive care units (NICU), there is limited evidence regarding the optimal time to commence PN in term and late preterm infants. The recommendations from the recently published ESPGHAN/ESPEN/ESPR/CPEN and NICE guidelines are substantially different in this area, and surveys have reported variations in clinical practice. The aim of this randomised controlled trial (RCT) is to evaluate the benefits and risks of early versus late PN in term and late preterm infants. Methods/design This study is a single-centre, non-blinded RCT in the NICU of Perth Children’s Hospital, Western Australia.A total of 60 infants born ≥34 weeks of gestation who have a high likelihood of intolerance to enteral nutrition (EN) for at least 3-5 days will be randomised to early (day 1 or day 2 of admission) or late commencement (day 6 of admission) of PN after informed parental consent. In both groups, EN will be commenced as early as clinically feasible. Primary outcomes are plasma phenylalanine and plasma F2-isoprostane levels on Day 4 and Day 8 of admission. Secondary outcomes are total and individual plasma amino acid profiles, plasma and red blood cell fatty acid profiles, in-hospital all-cause mortality, hospital-acquired infections, length of hospital/NICU stay, z scores and changes in z scores at discharge for weight, height and head circumference, time to full EN, duration of respiratory (mechanical, non-invasive) support, duration of inotropic support, the incidence of hyper and hypoglycaemia, incidence of metabolic acidosis, liver function, blood urea nitrogen, and C-reactive protein (CRP). Discussion This RCT will examine the effects of early versus late PN in term and late preterm infants by comparing key biochemical and clinical outcomes and has the potential to identify underlying pathways for beneficial or harmful effects related to the timing of commencement of PN in such infants. Trial registration ANZCTR; ACTRN12620000324910 (3rd March 2020)

Jingyi Shen,1,&ast; Huiyan Yu,1,&ast; Kaifeng Li,2 Bingjie Ding,3 Rong Xiao,1 Weiwei Ma1 1School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Nutrition and Metabolism Research Division, Innovation Center, Heilongjiang Feihe Dairy Co., Ltd., Beijing, 100015, People’s Republic of China; 3Department of Clinical Nutrition, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiwei Ma, School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, People’s Republic of China, Tel/Fax +86-10-83911651, Email weiweima@ccmu.edu.cnPurpose: To verify the mediating role of inflammatory factors in plasma fatty acid-induced changes in cognitive function in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: In this study, we evaluated the cognitive function of 372 Chinese patients (the average age was 58.00 (52.50, 63.00) years) with T2DM by using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), with plasma fatty acids measured by gas chromatography analysis and inflammatory cytokines determined by immune turbidimetric analysis and enzyme-linked immunosorbent assay (ELISA) to investigate whether there was a correlation between the plasma fatty acids, inflammatory cytokine levels and cognitive test scores in Chinese patients with T2DM.Results: We found that the increase of waist circumference and hip circumference might lead to cognitive impairment and induce the inflammatory response. Higher saturated fatty acids (SFAs) levels in plasma were linked to cognitive decline, while higher monounsaturated fatty acids (MUFAs) intake might be a protective factor for cognitive function. In addition, higher levels of plasma n-6 polyunsaturated fatty acids (n-6 PUFAs) stood out as having association with lower cognitive function scores, while higher level of plasma C22:6 n-3 could be a predictor of better cognitive function. In our study, higher SFAs led to higher proinflammatory factor levels. Apart from that, MUFAs and stearoyl-CoA desaturase-18 (SCD-18) were positively related to hypersensitive C-reactive protein (hs-CRP). Meanwhile, higher level of plasma C20:0 could lead to better MMSE delayed recall by reduce the expression of hs-CRP.Conclusion: Levels of plasma SFAs, C18:3 n-6, and C20:3 n-6 could be a predictor for worse cognitive function, while MUFAs and C22:6 n-3 could be a predictor for better cognitive function. The level of hs-CRP could be a mediator of C20:0 induced the change of cognitive function.Keywords: cognitive function, inflammatory cytokines, plasma fatty acids, T2DM, the mediation model

Background: Despite the wide use of parenteral nutrition (PN) in neonatal intensive care units (NICU), there is limited evidence regarding the optimal time to commence PN in term and late preterm infants. The recommendations from the recently published ESPGHAN/ESPEN/ESPR/CPEN and NICE guidelines are substantially different in this area, and surveys have reported variations in clinical practice. The aim of this randomised controlled trial (RCT) is to evaluate the benefits and risks of early versus late PN in term and late preterm infants.Methods/design: This study is a single-centre, non-blinded RCT in the NICU of Perth Children's Hospital, Western Australia.A total of 60 infants born ≥34 weeks of gestation who have a high likelihood of intolerance to enteral nutrition (EN) for at least 3-5 days will be randomised to early (day 1 or day 2 of admission) or late commencement (day 6 of admission) of PN after informed parental consent. In both groups, EN will be commenced as early as clinically feasible. Primary outcomes are plasma phenylalanine and plasma F2-isoprostane levels on Day 4 and Day 8 of admission. Secondary outcomes are total and individual plasma amino acid profiles, plasma and red blood cell fatty acid profiles, in-hospital all-cause mortality, hospital-acquired infections, length of hospital/NICU stay, z scores and changes in z scores at discharge for weight, height and head circumference, time to full EN, duration of respiratory (mechanical, non-invasive) support, duration of inotropic support, the incidence of hyper and hypoglycaemia, incidence of metabolic acidosis, liver function, blood urea nitrogen, and C-reactive protein (CRP).Discussion: This RCT will examine the effects of early versus late PN in term and late preterm infants by comparing key biochemical and clinical outcomes and has the potential to identify underlying pathways for beneficial or harmful effects related to the timing of commencement of PN in such infants.Trial Registration: ANZCTR; ACTRN12620000324910 (3rd March 2020). [ABSTRACT FROM AUTHOR]

The fruit juice industry generates pomace as a valuable by-product especially rich in polyphenols, dietary fibers, vitamins, minerals, and unsaturated fatty acids. In the cookies used in this study, 30% of the gluten-free flour was replaced with dried and ground blueberry and raspberry pomace, rich source of polyphenols, dietary fibers, linoleic and alpha-linolenic acid. In order to examine whether the addition of blueberry and raspberry pomace in cookie formulation can have beneficial effects on certain blood parameters and anthropometric measurements, the designed cookies were tested in 20 healthy, normally fed female subjects, aged 30–50 years (41.35 ± 8.58 years) over four-week dietetic intervention study. Significant changes in the composition of fatty acids serum phospholipids, decrease in LDL-cholesterol level (20.16%), increase in adiponectin level (25.52%) and decrease in ALT and AST values were observed, thus indicating that inclusion of cookies containing blueberry and raspberry dried and ground pomace to usual diet might have positive effects on certain cardiovascular risk factors and liver function indicators.

Abstract Background Circulating odd-chain fatty acids pentadecanoic (15:0) and heptadecanoic acid (17:0) are considered to reflect dairy intake. In cohort studies, higher circulating 15:0 and 17:0 were associated with lower type 2 diabetes risk. A recent randomized controlled trial in humans suggested that fiber intake also increased circulating 15:0 and 17:0, potentially resulting from fermentation by gut microbes. We examined the associations of dairy and fiber intake with circulating 15:0 and 17:0 in patients with a history of myocardial infarction (MI). Methods We performed cross-sectional analyses in a subsample of 869 Dutch post-MI patients of the Alpha Omega Cohort who had data on dietary intake and circulating fatty acids. Dietary intakes (g/d) were assessed using a 203-item food frequency questionnaire. Circulating 15:0 and 17:0 (as % of total fatty acids) were measured in plasma phospholipids (PL) and cholesteryl esters (CE). Spearman correlations (r s ) were computed between intakes of total dairy, dairy fat, fiber, and circulating 15:0 and 17:0. Results Patients were on average 69 years old, 78% was male and 21% had diabetes. Total dairy intake comprised predominantly milk and yogurt (69%). Dairy fat was mainly derived from cheese (47%) and milk (15%), and fiber was mainly from grains (43%). Circulating 15:0 in PL was significantly correlated with total dairy and dairy fat intake (both r s = 0.19, p

Background Habitual intake of long‐chain omega‐3 fatty acids, especially eicosapentaenoic and docosahexaenoic acid (EPA+DHA) from fish, has been associated with a lower risk of fatal coronary heart disease (CHD) in population‐based studies. Whether that is also the case for patients with CHD is not yet clear. We studied the associations of dietary and circulating EPA+DHA and alpha‐linolenic acid, a plant‐derived omega‐3 fatty acids, with long‐term mortality risk after myocardial infarction. Methods and Results We analyzed data from 4067 Dutch patients with prior myocardial infarction aged 60 to 80 years (79% men, 86% on statins) enrolled in the Alpha Omega Cohort from 2002 to 2006 (baseline) and followed through 2018. Baseline intake of fish and omega‐3 fatty acids were assessed through a validated 203‐item food frequency questionnaire and circulating omega‐3 fatty acids were assessed in plasma cholesteryl esters. Hazard ratios (HRs) with 95% CIs were obtained from Cox regression analyses. During a median follow‐up period of 12 years, 1877 deaths occurred, of which 515 were from CHD and 834 from cardiovascular diseases. Dietary intake of EPA+DHA was significantly inversely associated with only CHD mortality (HR, 0.69 [0.52–0.90] for >200 versus ≤50 mg/d; HR, 0.92 [0.86–0.98] per 100 mg/d). Similar results were obtained for fish consumption (HRCHD, 0.74 [0.53–1.03] for >40 versus ≤5 g/d; Ptrend: 0.031). Circulating EPA+DHA was inversely associated with CHD mortality (HR, 0.71 [0.53–0.94] for >2.52% versus ≤1.29%; 0.85 [0.77–0.95] per 1‐SD) and also with cardiovascular diseases and all‐cause mortality. Dietary and circulating alpha‐linolenic acid were not significantly associated with mortality end points. Conclusions In a cohort of Dutch patients with prior myocardial infarction, higher dietary and circulating EPA+DHA and fish intake were consistently associated with a lower CHD mortality risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03192410.

Background and Aims: Age-related kidney function decline is accelerated in patients with coronary heart disease (CHD). CHD and chronic kidney disease may share common etiologies. We examined plasma fatty acids (FAs) as novel biomarkers of kidney function decline after myocardial infarction (MI).Methods and Results: The analysis included 2329 Dutch post-MI patients aged 60-80y (Alpha Omega Cohort) most receiving state-of-the-art medications. Plasma FAs (% total FAs) in cholesteryl esters were assessed at baseline (2002-2006), and ∼40 months change in creatinine-cystatin C based glomerular filtration rate was estimated (eGFR, in ml/min per 1.73 m2). Beta coefficients for annual eGFR change in relation to plasma linoleic acid (LA; 50.1% of total FAs in CE), omega-3 FAs (EPA + DHA; 1.7%), odd-chain FAs (C15:0 and C17:0; 0.2%), and C14:0 (0.7%) were obtained from linear regression analyses adjusted for age, sex, smoking, and alcohol intake. Mean baseline eGFR ±SD was 78.5 ± 18.7, which declined by 4.7 ± 13.1 during follow-up, or 1.4 ± 3.9 per year. The annual decline in eGFR was less in patients with higher plasma LA (adjusted beta: 0.40 for LA >47 vs ≤ 47%, 95% CI: 0.01; 0.78; p = 0.046). Associations of plasma LA with annual eGFR decline were stronger in 437 patients with diabetes (1.21, 0.24; 2.19) and in 402 patients with CKD (eGFR<60; 0.90, -0.09; 1.89). Weaker, non-significant associations with kidney function decline were observed for the other plasma FAs.Conclusion: Higher plasma LA may be a good predictor of less kidney function decline after MI, particularly in patients with diabetes. The Alpha Omega Cohort is registered with clinicaltrials.gov, NCT03192410. [ABSTRACT FROM AUTHOR]

Aging leads to immune function changes which contribute to occurrence of chronic conditions. White blood cell (WBC) level is a marker widely known to reflect the immune function, thus, prediction of WBC level changes by using certain biomarkers is needed to prevent chronic conditions and to decrease the burdens of aging. In this respect, the present study aimed to explore the relationships between inflammatory markers and plasma fatty acid (FA) composition according to WBC levels for verifying potential predictors of WBC levels. Study subjects were divided into three groups according to their WBC count: moderate-low WBC (MLW), normal WBC, and moderate-high WBC (MHW). Inflammatory markers were measured, and plasma FA profiles were constructed via gas chromatography-mass spectrometry (GC-MS). In the MHW group, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), γ-glutamyltransferase (GGT), high-sensitivity C-reactive protein (hs-CRP), and interferon (IFN)-γ showed significant increases compared to those in the other groups. In addition, the granulocyte-to-lymphocyte ratio (GLR) significantly increased according to the WBC levels, whereas the platelet-to-lymphocyte ratio (PLR) showed the opposite result. Total ω-3 polyunsaturated fatty acids (PUFAs) showed significant differences among the groups. Regarding ω-6 PUFAs, dihomo-γ-linolenic acid and docosatetraenoic acid levels were significantly increased in the MHW group compared to the other groups. Finally, multivariate linear regression analysis revealed that GGT, hs-CRP, IFN-γ, ω-3 PUFAs, and dihomo-γ-linolenic acid were independent factors for altering WBC levels. In conclusion, elevated WBC levels accompanied by an increased GLR and a decreased PLR were associated with the risk of type 2 diabetes based on increased insulin and HOMA-IR levels and decreased adiponectin levels. Additionally, GGT, hs-CRP, IFN-γ, ω-3 PUFAs, and dihomo-γ-linolenic acid levels emerged as independent biomarkers for predicting WBC level alterations. Therefore, this study showed that these inflammatory markers and plasma FAs not only affect WBC level alterations but also may play roles in the risk of type 2 diabetes as one of the chronic conditions by certain mechanisms, which should be further studied. Finally, checking these biomarkers along with WBC levels can be helpful to prevent the chronic conditions.

The period from late gestation to early lactation is characterized by changes in energy metabolism. The aim of the current study was to analyze the plasma total lipid fraction using gas chromatography (GC) analysis, in order to highlight metabolic changes from the pre-foaling to post-foaling periods. Eleven pluriparous dairy jennies (mean age of 11.88 ± 3.79 years) belonging to the Amiata donkey breed were enrolled. Blood sampling was performed at 15 days before foaling (T0), and 15 (T1), 30 (T2), 60 (T3), and 90 (T4) days after foaling, for biochemical and GC analysis. A total of 37 fatty acids were identified in plasma samples: 4 medium chain (MCFA), 24 long chain (LCFA), and 9 very-long chain (VLCFA) fatty acids. Among them, 20 fatty acids changed significantly, and two fatty acid showed a trend toward significance. Furthermore, the LCFA, saturated, unsaturated, monounsaturated, and polyunsaturated ω-3 fatty acids changed significantly during the study period. The main alterations were between T0 and the other time points and appeared to be related to lipid metabolism, cellular structure and function, and inflammatory and immune responses. Our findings reveal greater energy requirements at the end of gestation compared to early lactation in donkeys.

Abstract Background Solid evidence indicates that intake of marine n-3 fatty acids lowers serum triglycerides and that replacing saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFA) reduces plasma total cholesterol and LDL cholesterol. The molecular mechanisms underlying these health beneficial effects are however not completely elucidated. The aim of this study was therefore to investigate the expression of genes related to lipid metabolism in peripheral blood mononuclear cells (PBMC) depending on the plasma levels of n-6 and n-3 fatty acids and the SFA to PUFA ratio. Methods Fifty-four healthy subjects were grouped into tertiles (n = 18) based on plasma levels of n-6 and n-3 fatty acids and the SFA to PUFA ratio. The PBMC gene expression levels among subjects in the highest versus the lowest tertiles were compared. In total, 285 genes related to cholesterol and triglyceride metabolism were selected for this explorative study. Results Among the 285 selected genes, 161 were defined as expressed in the PBMCs. The plasma SFA to PUFA ratio was associated with the highest number of significantly different expressed genes (25 gene transcripts), followed by plasma n-6 fatty acid level (15 gene transcripts) and plasma n-3 fatty acid level (8 gene transcripts). In particular, genes involved in cholesterol homeostasis were significantly different expressed among subjects with high compared to low plasma SFA to PUFA ratio. Conclusion Genes involved in lipid metabolism were differentially expressed in PBMCs depending on the plasma fatty acid levels. This finding may increase our understanding of how fatty acids influence lipid metabolism at a molecular level in humans.

Aims/hypothesis: This biomarker study aimed to quantify the association of essential and other plasma fatty acid biomarkers with macrovascular disease, microvascular disease and death in individuals with type 2 diabetes. Methods: A case-cohort study (N = 3576), including 654 macrovascular events, 341 microvascular events and 631 deaths during 5 years of (median) follow-up, was undertaken as a secondary analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) study (full details of the study design and primary endpoints of the ADVANCE trial and its case-cohort have been published previously). This current study considers new data: fatty acids measured from baseline plasma samples by proton NMR analysis. The fatty acids measured were n-3, docosahexaenoic acid (DHA), n-6, linoleic acid, and polyunsaturated, monounsaturated and saturated fatty acids. HRs were modelled per SD higher (percentage) fatty acid. C statistics and continuous net reclassification improvement were used to test the added value of fatty acids compared with traditional cardiovascular risk factors. Results: After adjustment for traditional cardiovascular risk factors, an inverse association was observed for n-3 fatty acids and DHA with the risk of macrovascular events (HR [95% CI]: 0.87 [0.80, 0.95] and 0.88 [0.81, 0.96], respectively, per 1 SD higher percentage), and for n-3 fatty acids with the risk of death (HR 0.91 [95% CI 0.84, 0.99] per 1 SD higher percentage). Such associations were also evident when investigating absolute levels of fatty acids. There were no statistically significant associations between any fatty acids and microvascular disease after adjustment. However, there was limited improvement in the predictive ability of models when any fatty acid was added. Conclusions/interpretation: Plasma n-3 fatty acids and DHA were found to be inversely associated with macrovascular disease, while n-3 fatty acids were also inversely associated with death. These results support the cardioprotective effects of n-3 fatty acids and DHA and further merit testing the role of high-dose supplementation with n-3 fatty acids in individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT00145925. [ABSTRACT FROM AUTHOR]

Aging leads to immune function changes which contribute to occurrence of chronic conditions. White blood cell (WBC) level is a marker widely known to reflect the immune function, thus, prediction of WBC level changes by using certain biomarkers is needed to prevent chronic conditions and to decrease the burdens of aging. In this respect, the present study aimed to explore the relationships between inflammatory markers and plasma fatty acid (FA) composition according to WBC levels for verifying potential predictors of WBC levels. Study subjects were divided into three groups according to their WBC count: moderate-low WBC (MLW), normal WBC, and moderate-high WBC (MHW). Inflammatory markers were measured, and plasma FA profiles were constructed via gas chromatography-mass spectrometry (GC-MS). In the MHW group, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), γ-glutamyltransferase (GGT), high-sensitivity C-reactive protein (hs-CRP), and interferon (IFN)-γ showed significant increases compared to those in the other groups. In addition, the granulocyte-to-lymphocyte ratio (GLR) significantly increased according to the WBC levels, whereas the platelet-to-lymphocyte ratio (PLR) showed the opposite result. Total ω-3 polyunsaturated fatty acids (PUFAs) showed significant differences among the groups. Regarding ω-6 PUFAs, dihomo-γ-linolenic acid and docosatetraenoic acid levels were significantly increased in the MHW group compared to the other groups. Finally, multivariate linear regression analysis revealed that GGT, hs-CRP, IFN-γ, ω-3 PUFAs, and dihomo-γ-linolenic acid were independent factors for altering WBC levels. In conclusion, elevated WBC levels accompanied by an increased GLR and a decreased PLR were associated with the risk of type 2 diabetes based on increased insulin and HOMA-IR levels and decreased adiponectin levels. Additionally, GGT, hs-CRP, IFN-γ, ω-3 PUFAs, and dihomo-γ-linolenic acid levels emerged as independent biomarkers for predicting WBC level alterations. Therefore, this study showed that these inflammatory markers and plasma FAs not only affect WBC level alterations but also may play roles in the risk of type 2 diabetes as one of the chronic conditions by certain mechanisms, which should be further studied. Finally, checking these biomarkers along with WBC levels can be helpful to prevent the chronic conditions. [ABSTRACT FROM AUTHOR]

Elevated lipoprotein(a) (Lp(a)) is associated with CVD and is mainly genetically determined. Studies suggest a role of dietary fatty acids (FA) in the regulation of Lp(a); however, no studies have investigated the association between plasma Lp(a) concentration and n -6 FA. We aimed to investigate whether plasma Lp(a) concentration was associated with dietary n -6 FA intake and plasma levels of arachidonic acid (AA) in subjects with familial hypercholesterolaemia (FH). We included FH subjects with (n 68) and without (n 77) elevated Lp(a) defined as ≥75 nmol/l and healthy subjects (n 14). Total FA profile was analysed by GC–flame ionisation detector analysis, and the daily intake of macronutrients (including the sum of n -6 FA: 18 : 2 n -6, 20 : 2 n -6, 20 : 3 n -6 and 20 : 4 n -6) were computed from completed FFQ. FH subjects with elevated Lp(a) had higher plasma levels of AA compared with FH subjects without elevated Lp(a) (P = 0·03). Furthermore, both FH subjects with and without elevated Lp(a) had higher plasma levels of AA compared with controls (P < 0·001). The multivariable analyses showed associations between dietary n -6 FA intake and plasma levels of AA (P = 0·02) and between plasma levels of Lp(a) and AA (P = 0·006). Our data suggest a novel link between plasma Lp(a) concentration, dietary n -6 FA and plasma AA concentration, which may explain the small diet-induced increase in Lp(a) levels associated with lifestyle changes. Although the increase may not be clinically relevant, this association may be mechanistically interesting in understanding more of the role and regulation of Lp(a). [ABSTRACT FROM AUTHOR]

Background and Aims: Population-based studies often use plasma fatty acids (FAs) as objective indicators of FA intake, especially for n-3 FA and linoleic acid (LA). The relation between dietary and circulating FA in cardiometabolic patients is largely unknown. We examined whether dietary n-3 FA and LA were reflected in plasma lipid pools in post-myocardial infarction (MI) patients.Methods and Results: Patients in Alpha Omega Cohort filled out a 203-item food-frequency questionnaire from which eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), and LA intake were calculated. Circulating individual FA (% total FA) were assessed in cholesteryl esters (CE; n = 4066), phospholipids (PL; n = 838), and additionally in total plasma for DHA and LA (n = 739). Spearman correlation coefficients (rs) were calculated for dietary vs. circulating FA. Circulating FA were also compared across dietary FA quintiles, overall and in subgroups by sex, obesity, diabetes, statin use, and high alcohol intake. Patients were on average 69 years old and 79% was male. Moderate correlations between dietary and circulating levels were observed for EPA (rs∼0.4 in CE and PL) and DHA (rs ∼0.5 in CE and PL, ∼0.4 in total plasma), but not for ALA (rs ∼0.0). Weak correlations were observed for LA (rs 0.1 to 0.2). Plasma LA was significantly lower in statin users and in patients with a high alcohol intake.Conclusions: In post-MI patients, dietary EPA and DHA were well reflected in circulating levels. This was not the case for LA, which may partly be influenced by alcohol use and statins. [ABSTRACT FROM AUTHOR]

Since the lipid profile is altered by physical activity, the study of lipid metabolism is a remarkable element in understanding if and how physical activity affects the health of both professional athletes and sedentary subjects. Although not fully defined, it has become clear that resistance exercise uses fat as an energy source. The fatty acid oxidation rate is the result of the following processes: (a) triglycerides lipolysis, most abundant in fat adipocytes and intramuscular triacylglycerol (IMTG) stores, (b) fatty acid transport from blood plasma to muscle sarcoplasm, (c) availability and hydrolysis rate of intramuscular triglycerides, and (d) transport of fatty acids through the mitochondrial membrane. In this review, we report some studies concerning the relationship between exercise and the aforementioned processes also in light of hormonal controls and molecular regulations within fat and skeletal muscle cells.

This article reports a targeted metabolomic method for total plasma fatty acids (FAs) of clinical or nutritional relevance. Thirty-six saturated, unsaturated, or branched-chain FAs with a chain length of C8-C28 were quantified using reversed-phase liquid chromatography-tandem mass spectrometry. FAs in plasma (10 μL) were acid-hydrolyzed, extracted, and derivatized with DAABD-AE (4-[2-(N,N-Dimethylamino)ethylaminosulfonyl]-7-(2-aminoethylamino)-2,1,3-benzoxadiazole) at 60 °C for 1 h. Derivatization resulted in a staggering nine orders of magnitude higher sensitivity compared to underivatized analytes. FAs were measured by multiple-reaction monitoring using stable isotope internal standards. With physiological and pathological analyte levels in mind, linearity was established using spiked plasma. Intra-day (n = 15) and inter-day (n = 20) imprecisions expressed as variation coefficient were ≤10.2% with recovery ranging between 94.5–106.4%. Limits of detection and limit of quantitation ranged between 4.2–14.0 and 15.1–51.3 pmol per injection, respectively. Age-stratified reference intervals were established in four categories: 18 year. This method was assessed using samples from patients with disorders affecting FAs metabolism. For the first time, C28:0 and C28:0/C22:0 ratio were evaluated as novel disease biomarkers. This method can potentially be utilized in diagnosing patients with inborn errors of metabolism, chronic disease risk estimation, or nutritional applications.

Changes in plasma fatty acid (FA) composition and desaturase activities are observed in metabolic syndrome (MS). However, whether these changes are a reflection of dietary intakes of fats and FAs is not well established. The current study was aimed at assessing plasma FA composition and desaturase enzyme activities as biomarkers of dietary intakes in subjects with MS. Case control study was done on 41 MS patients and was compared with age matched 45 controls. Dietary intakes, anthropometric and clinical parameters were measured. FA composition was analysed using gas chromatography-flame ionisation detector and desaturase enzyme activities were estimated as ratios of product to precursor FAs. Higher levels of 14:0, 16:0, 16:1, 18:1, D9D-18 activity and lower levels of 18:0 and 18:2 n-6 were seen in MS group when compared to controls (p < 0.05). Strong positive correlations were seen between plasma triglyceride (TG) levels and 14:0, 16:0, 16:1, 18:1, total saturated fatty acid, total monounsaturated fatty acid, and D9D activities, while 18:0, 18:2 n-6 and total polyunsaturated fatty acid were negatively correlated with TG. Positive correlations were seen between plasma 14:0, 18:1 and D9D-18 activity with total energy intake and carbohydrate (CHO) intakes but not with fat intake. Plasma FA profile appears to be a better index of total energy intake and CHO intake than fat intake, suggesting it might be a good reflection of endogenous FA metabolism. Changes in FA composition may therefore serve as an early index of dysregulation of FA metabolism, resulting in increased risk of MS. [ABSTRACT FROM AUTHOR]

Background: We have previously reported that patients with Crohn’s disease (CD) have a very specific erythrocyte membrane phospholipid fatty acid profile. The findings of this study suggest that the activities of enzymes involved in the metabolism of linoleic acid (LA), that is, delta-6 desaturase, are higher in CD patients than in healthy individuals. Methods: We evaluated the utilities of various fatty acid compositions of the plasma (p-) as new serological markers for CD compared to those of erythrocyte membranes (e-). Results: Fifty CD patients and 50 healthy individuals were enrolled. In both plasma and erythrocyte membranes, the weight percentages of palmitic acid (PA) were significantly higher, while those of LA were significantly lower in CD patients than in controls. Fatty acids with high sensitivity and specificity were p-PA (0.86 and 0.74) and e-PA (0.80 and 0.74). With PA and LA as a CD fatty acid index (CDFAi), that is, CDFAi = (PA/LA), the sensitivity and specificity of plasma CDFAi (p-CDFAi) and e-CDFAi were 0.80 and 0.80; and 0.82 and 0.88 respectively. Conclusion: In CD patients, various fatty acids were specifically altered in both plasma and erythrocytes, and p-PA and p-CDFAi are potentially useful as new serological markers for CD. [ABSTRACT FROM AUTHOR]

Background While dietary fat has been established as a risk factor for colorectal cancer (CRC), associations between fatty acids (FAs) and CRC have been inconsistent. Using Mendelian randomisation (MR), we sought to evaluate associations between polyunsaturated (PUFA), monounsaturated (MUFA) and saturated FAs (SFAs) and CRC risk. Methods We analysed genotype data on 9254 CRC cases and 18,386 controls of European ancestry. Externally weighted polygenic risk scores were generated and used to evaluate associations with CRC per one standard deviation increase in genetically defined plasma FA levels. Results Risk reduction was observed for oleic and palmitoleic MUFAs (OR OA = 0.77, 95% CI: 0.65–0.92, P = 3.9 × 10 −3 ; OR POA = 0.36, 95% CI: 0.15–0.84, P = 0.018). PUFAs linoleic and arachidonic acid had negative and positive associations with CRC respectively (OR LA = 0.95, 95% CI: 0.93–0.98, P = 3.7 × 10 −4 ; OR AA = 1.05, 95% CI: 1.02–1.07, P = 1.7 × 10 −4 ). The SFA stearic acid was associated with increased CRC risk (OR SA = 1.17, 95% CI: 1.01–1.35, P = 0.041). Conclusion Results from our analysis are broadly consistent with a pro-inflammatory FA profile having a detrimental effect in terms of CRC risk. [ABSTRACT FROM AUTHOR]

The assessment of diets in multi-ethnic cosmopolitan settings is challenging. A semi-quantitative 163-item food frequency questionnaire (FFQ) was developed for the adult Singapore population, and this study aimed to assess its reproducibility and relative validity against 24-h dietary recalls (24 h DR) and biomarkers. The FFQ was administered twice within a six-month interval in 161 adults (59 Chinese, 46 Malay, and 56 Indian). Fasting plasma, overnight urine, and 24 h DR were collected after one month and five months. Intra-class correlation coefficients between the two FFQ were above 0.70 for most foods and nutrients. The median correlation coefficient between energy-adjusted deattenuated FFQ and 24 h DR nutrient intakes was 0.40 for FFQ1 and 0.39 for FFQ2, highest for calcium and iron, and lowest for energy and carbohydrates. Significant associations were observed between urinary isoflavones and soy protein intake (r = 0.46), serum carotenoids and fruit and vegetable intake (r = 0.34), plasma eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) and fish/seafood intake (r = 0.36), and plasma odd chain saturated fatty acids (SFA) and dairy fat intake (r = 0.25). Associations between plasma EPA + DHA and fish/seafood intake were consistent across ethnic groups (r = 0.28-0.49), while differences were observed for other associations. FFQ assessment of dietary intakes in modern cosmopolitan populations remains feasible for the purpose of ranking individuals' dietary exposures in epidemiological studies. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the relationship of four TNF-α SNP with inflammatory biomarkers and plasma fatty acids (FA), and the interaction among them in a population-based, cross-sectional study in São Paulo, Brazil. A total of 281 subjects, aged >19 and <60 years, participated in a cross-sectional, population-based study performed in Brazil. The following SNP spanning the TNF-α gene were genotyped: -238G/A (rs361525), -308G/A (rs1800629), -857C/T (rs1799724) and -1031T/C (rs1799964). In all, eleven plasma inflammatory biomarkers and plasma FA profile were determined. To analyse the interaction between TNF-α SNP and plasma FA, a cluster analysis was performed to stratify individuals based on eleven inflammatory biomarkers into two groups used as outcome: inflammatory (INF) and non-inflammatory clusters. The -238A allele carriers had higher TNF-α (P=0·033), IL-6 (P=0·013), IL-1β (P=0·037), IL-12 (0·048) and IL-10 (P=0·010) than the GG genotype. The -308A allele carriers also had lower levels of plasma palmitoleic acid (P=0·009), oleic acid (P=0·039), total MUFA (P=0·014), stearoyl-CoA desaturase (SCD) activity index-16 (P=0·007), SCD-18 (P=0·020) and higher levels of PUFA (P=0·046) and DHA (P=0·044). Significant interactions modifying the risk of belonging to the INF cluster were observed with inflammatory cluster as outcome between -857C/T and plasma α-linolenic acid (P=0·026), and also between -308G/A and plasma stearic acid (P=0·044) and total SFA (P=0·040). Our study contributes to knowledge on TNF-α SNP and their association with inflammatory biomarker levels, plasma FA and the interaction among them, of particular interest for the Brazilian population. [ABSTRACT FROM AUTHOR]

Experimental animal models are the primary tool to test nutritional intervention strategies for health promotion and prevention and/or treatment of human diseases. These kinds of experiments test hypotheses that otherwise could not be done in humans. These models generate data important for pre-clinical screening purposes. However their ability to predict human responses has been disappointing, particularly when it comes to dietary n-3 and n-6 polyunsaturated fatty acids (PUFA). Many times it is difficult to recapitulate the data as a result of diet between pre-clinical experiments and clinical trials in part because we lack the fundamental understanding of how to effectively translate diets between species. The diets in experiments using rodent models are preferentially designed to generate positive results (i.e., perform a dose response and pick the dose that works) with little thought on their applicability to humans. Accordingly, the levels of n-3 and n-6 PUFA used in rodent diets are typically on the extreme and rarely justified. A search of the literature reveals no guidelines establishing appropriate levels for the use of PUFA in rodent diets although extrapolation to human conditions is quite common despite being inappropriate. The goal of this paper is to examine allometric scaling models between species for dietary PUFA using similar endpoints with the hypothesis that equivalent physiological changes in rodents and humans support the mathematical model. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether moderate differences in dietary carbohydrate quantity and quality influence plasma FAs in the lipogenic pathway in healthy adults., Objectives: We investigated the effects of different carbohydrate quantities and quality on plasma palmitate concentrations (primary outcome) and other saturated and MUFAs in the lipogenic pathway., Methods: Twenty healthy participants were randomly assigned, and 18 (50% women; age: 22-72 y; BMI: 18.2-32.7 kg/m 2 and BMI was measured in kg/m 2 ) started the cross-over intervention. During each 3-wk period (separated by a 1-wk washout period), 3 diets were consumed (all foods provided) in random order: low-carbohydrate (LC) (38% energy (E) carbohydrates, 25-35 g fiber/d, 0% E added sugars); high-carbohydrate/high-fiber (HCF) (53% E carbohydrates, 25-35 g fiber/d, 0% E added sugars); and high-carbohydrate/high-sugar (HCS) (53% E carbohydrates, 19-21 g fiber/d, 15% E added sugars). Individual FAs were measured proportionally to total FAs by GC in plasma cholesteryl esters, phospholipids, and TGs. False discovery rate-adjusted repeated measures ANOVA [ANOVA-false discovery rate (FDR)] was used to compare outcomes., Results: The self-reported intakes of carbohydrates and added- and free sugars were; 30.6% E and 7.4% E in LC, 41.4% E and 6.9% E in HCF, and 45.7% E and 10.3% in HCS. Plasma palmitate did not differ between the diet periods (ANOVA FDR P > 0.43, n = 18). After HCS, myristate concentrations in cholesterol esters and phospholipids were ≥19% higher than LC and ≥22% higher than HCF (P = 0.005). After LC, palmitoleate in TG was 6% lower compared with HCF and 7% compared with HCS (P = 0.041). Body weight differed (≤0.75 kg) between diets before FDR correction., Conclusions: Different carbohydrate quantity and quality do not influence plasma palmitate concentrations after 3 wk in healthy Swedish adults, whereas myristate increased after the moderately higher intake of carbohydrate/high-sugar, but not carbohydrate/high-fiber. Whether plasma myristate is more responsive than palmitate to differences in carbohydrate intake requires further study, especially considering that participants deviated from the planned dietary targets. J Nutr 20XX;xx:xx-xx. This trial was registered at clinicaltrials.gov as NCT03295448., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective Absorption of long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to be potentiated when consumed with a high fat meal. However, the effect of different dietary fats on n-3PUFA absorption and postprandial kinetics has not been previously studied. Method In a randomized cross-over design intervention, postprandial incorporation of LCn-3PUFA into plasma lipids following consumption of a meal rich in either saturated fat or omega-6 polyunsaturated fatty acids (n-6PUFA) was investigated. Healthy adult male and female subjects (n = 26) were fed an isocaloric meal containing equivalent amount of either butter or sunflower seed oil supplemented with 1.8 grams of LCn-3PUFA (300 mg eicosapentaenoic acid, 20:5n-3 and 1500 mg docosahexaenoic acid, 22:6n-3). Results Postprandial plasma lipids were enriched with saturated fatty acids and linoleic acid (18:2n-6) following consumption of the butter and the sunflower oil containing meals respectively. The increase in plasma 20:5n-3 and 22:6n-3 levels over the 6 hour study period was similar in both the saturated and the n-6 fat groups. Conclusion These results suggest that the expected competition between LCn-3PUFA and n-6PUFA at the absorption level is unlikely; therefore competition at the enzymatic level should be primarily responsible for differences in their metabolic and clinical effects. Trial registered with the Australia New Zealand Trial registry as ACTRN12612000654853. [ABSTRACT FROM AUTHOR]

The type of diet consumed by individuals has been associated with the development of some chronic diseases, including cardiovascular disease (CVD), cancer, diabetes, and others. Populations that consume diets rich in fruits and vegetables and drink wine in moderation, as the Mediterranean, have a higher life expectancy and less chronic diseases than other occidental populations. We carried out an intervention study in humans to evaluate the effect of a Mediterranean diet (MD), an Occidental diet (OD) and their supplementation with red wine, on biochemical, physiological and clinical parameters related to atherosclerosis and other chronic diseases. For 3 months, two groups of 21 male volunteers each, received either a MD or an OD; during the second month, red wine was added isocalorically, 240 ml/day. At days 0, 30, 60 and 90, clinical, physiological and biochemical evaluations were made. In this article we report on the results obtained in plasma fatty acids profile that includes saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), w-6 fatty acids, w-3 fatty acids and w-6/w-3 ratio. Other results have been published previously. Plasma fatty acid percentages in the OD group, compared to the MD group, did not show differences in SFA, but the OD group showed lower levels of MUFA and w-3 fatty acids, and higher levels of PUFA and w-6 fatty acids, with a higher w-6/w-3 ratio than the MD group. Wine supplementation reduced MUFA and increased PUFA in both dietary groups, suggesting that wine could improve a diet with a good w-6/w-3 ratio. Volunteers on MD showed a better fatty acid profile than those on OD, suggesting a lower cardiovascular risk. Moderate consumption of wine improves this profile in the MD group.

The assessment of diets in multi-ethnic cosmopolitan settings is challenging. A semi-quantitative 163-item food frequency questionnaire (FFQ) was developed for the adult Singapore population, and this study aimed to assess its reproducibility and relative validity against 24-h dietary recalls (24 h DR) and biomarkers. The FFQ was administered twice within a six-month interval in 161 adults (59 Chinese, 46 Malay, and 56 Indian). Fasting plasma, overnight urine, and 24 h DR were collected after one month and five months. Intra-class correlation coefficients between the two FFQ were above 0.70 for most foods and nutrients. The median correlation coefficient between energy-adjusted deattenuated FFQ and 24 h DR nutrient intakes was 0.40 for FFQ1 and 0.39 for FFQ2, highest for calcium and iron, and lowest for energy and carbohydrates. Significant associations were observed between urinary isoflavones and soy protein intake (r = 0.46), serum carotenoids and fruit and vegetable intake (r = 0.34), plasma eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) and fish/seafood intake (r = 0.36), and plasma odd chain saturated fatty acids (SFA) and dairy fat intake (r = 0.25). Associations between plasma EPA + DHA and fish/seafood intake were consistent across ethnic groups (r = 0.28–0.49), while differences were observed for other associations. FFQ assessment of dietary intakes in modern cosmopolitan populations remains feasible for the purpose of ranking individuals’ dietary exposures in epidemiological studies.

Objectives: To determine the dietary and supplement intake of omega-3 (n-3) polyunsaturated fatty acids (PUFA) of older Tasmanian adults; their plasma n-3 PUFA status and the relationship between n-3 PUFA intake and plasma status. Design: Cross-sectional study. Setting: Launceston and surrounding regions, Tasmania, Australia. Participants: Seventy-three community-dwelling older adults: 23 men aged 70 ± 6.1 years and 50 women aged 70 ± 6.7 years. Measurements: A validated, semi-quantitative food frequency questionnaire estimated dietary PUFA intake. The plasma phospholipid fraction of venous blood samples was analysed for fatty acid content. Anthropometric data was recorded. Results: Thirty-five participants (48%) regularly ingested a fish oil supplement. Their plasma n-3 PUFA profile contained significantly more eicosapentaenoic acid (EPA) (odds ratio 3.14; 95% CI 1.37% to 7.30%; p<0.05) and docosahexaenoic acid (DHA) (odds ratio 2.64; 95% CI 1.16% to 6.01%; p<0.05) than non-supplement users. Fish and meat were the main dietary sources of n-3 PUFAs. Participants most commonly consumed fish 3-4 times per week. Significant associations of dietary α-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA) and DHA with plasma n-3 PUFAs were noted but not always between dietary and plasma counterparts. Conclusion: Without the use of fish oil supplements, most study participants were unable to meet the recommended daily intake of 0.5g EPA and DHA combined; however, the plasma n-3 PUFA profile of non-supplement-users was still robust compared to other Australian and overseas studies. [ABSTRACT FROM AUTHOR]

Lifestyle changes in Alaskan Natives have been related to the increase of cardiovascular disease and metabolic syndrome in the last decades. Variation of the apolipoprotein E (Apo E) genotype may contribute to the diverse response to diet in lipid metabolism and influence the association between fatty acids in plasma and risk factors for cardiovascular disease. The aim of this investigation was to analyze the interaction between Apo E isoforms and plasma fatty acids, influencing phenotypes related to metabolic diseases in Alaskan Natives. A sample of 427 adult Siberian Yupik Alaskan Natives was included. Fasting glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, Apo A1, and Apo B plasma concentrations were measured using reference methods. Concentrations of 13 fatty acids in fasting plasma were analyzed by gas chromatography, and Apo E variants were identified. Analyses of covariance were conducted to identify Apo E isoform and fatty acid main effects and multiplicative interactions. The means for body mass index and age were 26 ± 5.2 and 47 ± 1.5, respectively. Significant main effects were observed for variation in Apo E and different fatty acids influencing Apo B levels, triglycerides, and total cholesterol. Significant interactions were found between Apo E isoform and selected fatty acids influencing total cholesterol, triglycerides, and Apo B concentrations. In summary, Apo E3/3 and 3/4 isoforms had significant interactions with circulating levels of stearic, palmitic, oleic fatty acids, and phenotypes of lipid metabolism in Alaskan Natives. [ABSTRACT FROM AUTHOR]

Background: Plasma fatty acids (FAs) and micronutrients have been associated with central obesity in adults; however, previous studies of these associations in adults have yielded mixed results. In addition, no comparable research has been conducted among youth with type 1 diabetes (T1D). Objective: We investigated the cross-sectional and longitudinal associations between plasma nutrient biomarkers and waist-to-height ratio (WHtR) in youth with T1D. Methods: These analyses included 1324 youth aged 3-20 y at T1D diagnosis with a baseline visit in the SEARCH (Search for Diabetes in Youth) Study and a subset of 1178 of these youth with a follow-up visit an average of 23 mo (range: 16-40 mo) after their baseline visit. Plasma phospholipid FAs and vitamins were measured, and estimated desaturase activities were calculated at baseline. Anthropometric measurements and diabetes-related assessments were collected at each visit. Multiple linear regression was used to examine the association between plasma nutrient biomarkers and WHtR. Results: In cross-sectional analysis, plasma palmitic acid (P = 0.004), dihomo-γ-linolenic acid (DGLA; P = 0.017) and Δ6 desaturase (D6D; P = 0.006) were positively correlated with WHtR after adjustment of confounders. Oleic acid (OA; P = 0.002), linoleic acid (LA; P = 0.015), D9 desaturase 18 (D9D-18; P = 0.027), and vitamin D (P < 0.0001) were negatively correlated with WHtR after adjustment. Weight status was an effect modifier (P < 0.05). In normal-weight youth, vitamin D (P = 0.003) was negatively associated with WHtR. In obese youth, stearic acid (P = 0.037), DGLA (P < 0.0001), and D6D (P < 0.0001) were positively associated and OA (P = 0.0008), D9D-18 (P = 0.0006), and vitamin D (P < 0.0001) were negatively associated with WHtR. In longitudinal analysis, baseline linoleic acid (P = 0.018), n-6:n-3 (ω-3:ω-6) FA ratio (P = 0.029), vitamin D (P = 0.003), and vitamin E (P < 0.0001) were negatively correlated with WHtR at follow-up only in obese participants. Conclusions: In T1D youth, plasma FAs and vitamins are associated with WHtR and are modified by weight status. These associations are particularly marked in obese youth. [ABSTRACT FROM AUTHOR]

Mass spectrometry is an ideal tool for investigations of the metabolome in human plasma. To investigate the impact of smoking on the human metabolome, we performed an untargeted metabolic fingerprinting using GC-TOF-MS with EDTA-plasma samples from 25 smokers and 25 non-smokers. The observed elevated levels in the monounsaturated fatty acids (MUFAs) in smokers were verified by a targeted analysis using GC-FID, which revealed also significantly alterations in saturated and polyunsaturated fatty acids in smokers (p<0.05, Mann-Whitney U test). Since the main fraction of fatty acids in plasma is esterified to phospholipids, we analyzed phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species composition in the plasma samples of the same subjects. The profiles of 39 PC and 40 PE species were analyzed with a newly developed and validated HILIC-ESI-MS/MS method. We were able to baseline separate the two lipid classes (PC from PE) by maintaining co-elution of individual lipid species of each class. The method shows a linear range from 0.5µM to 2000µM and an inter- and intraday coefficient of variation (CV)<20% across all analytes. Application of the validated method to the plasma samples of smokers and non-smokers, derived from a diet-controlled smoking study, revealed significantly elevated levels of PC and PE species containing MUFAs in smokers. In summary, we could demonstrate that there is a significantly altered total fatty acid profile, with increased MUFAs, in the plasma of smokers compared to non-smokers. Results obtained with the new HILIC-MS/MS method indicate that the altered fatty acid profile is also reflected in the PC and PE profile of smokers. [ABSTRACT FROM AUTHOR]

Abstract: Background: Plasma levels of polyunsaturated fatty acids (PUFAs) are different before and after periodontal treatment. Asians and Westerners have significantly different baseline levels of plasma PUFAs. However, no Asian study has reported the effects of nonsurgical treatment on the correlation between periodontal condition and plasma levels of PUFAs. We analyzed whether recovery from periodontitis was correlated with the elevation of plasma fatty acids 3 months after the nonsurgical intervention and with no recommended supplements. Design: Thirty-five Taiwanese patients with periodontitis were recruited. Probing pocket depths (PPDs) and clinical attachment levels (CALs) were measured at baseline and 3 months after the nonsurgical treatment. Plasma levels of fatty acids were determined using gas chromatography. Differences and correlations between plasma fatty acid composition and periodontitis severity at baseline and 3 months after treatment were determined. Results: Twenty-six patients completed the study. At the baseline, PPDs were negatively correlated with plasma n-3 PUFAs (r =−0.52, p <0.01), but at 3 months post intervention, periodontitis severity had declined and the weight percentages of n-3 PUFAs, DPA, and DHA were significantly (p =0.019, 0.005, and 0.037, respectively) higher. The recovery percentages of CALs were positively and significantly correlated with plasma ΔPUFAs and the percentage of Δn-3 PUFAs in ΔPUFAs (r =0.42 and 0.45, respectively; p <0.05 for both). Conclusions: We conclude that a higher weight percentage of n-3 PUFAs in total PUFAs was related to the recovery of CALs 3 months after the nonsurgical periodontal treatment. However, no such relationship was found for PPDs. [Copyright &y& Elsevier]

Background and aims Differences in blood fatty acids (FAs) profile among populations with different lifestyle have partly been attributed to differences in food intake. A holistic approach in dietary guidance through dietary patterns is essential. This study aimed at evaluating the main plasma and red blood cell (RBC) FAs in three European populations and assessing the role of dietary patterns in explaining variation in their levels. Methods In the framework of the IMMIDIET Project, 1604 subjects (802 male-female pairs) aged 26-65 years were enrolled in Italy, Belgium and UK. Plasma and RBC FAs were measured. One year recall food frequency questionnaires were used to evaluate dietary habits of each individual. Results Italian cohort showed lower plasma and RBC n - 3 levels than participants of the other two populations (P < 0.001). Both plasma and RBC arachidonic acid were higher in Italian cohort as compared to Belgian and English. Reduced rank regression analysis indicated two dietary patterns explaining 35% and 17% of the total variation of the sum of plasma and RBC n - 3, respectively. In a holistic dietary analysis, neither fish nor mollusks intake seemed to contribute to n - 3 variation as compared to vegetable oils and polyphenol-rich foods. Conclusion The Italian cohort presented significant lower plasma and RBC n - 3 FA levels compared to Belgians and English. A holistic approach in dietary analysis seemed to explain a relatively high proportion of plasma and RBC n - 3 FAs variability. Dietary pattern analysis may contribute to the study of the association of human diet with FAs levels. [ABSTRACT FROM AUTHOR]

Background The Canola Oil Multicenter Intervention Trial (COMIT) was a randomized controlled crossover study designed to evaluate the effects of five diets that provided different oils and/or oil blends on cardiovascular disease (CVD) risk factors in individuals with abdominal obesity. The present objective is to report preliminary findings on plasma fatty acid profiles in volunteers with abdominal obesity, following the consumption of diets enriched with n-3, n-6 and n-9 fatty acids. Methods COMIT was conducted at three clinical sites, Winnipeg, Manitoba, Canada, Québec City, Québec, Canada and University Park, Pennsylvania, United States. Inclusion criteria were at least one of the followings: waist circumference (⩾90 cm for males and ⩾84 cm for females), and at least one other criterion: triglycerides ⩾1.7 mmol/L, high density lipoprotein cholesterol <1 mmol/L (males) or <1.3 mmol/L (females), blood pressure ⩾130 mmHg (systolic) and/or ⩾85 mmHg (diastolic), and glucose ⩾5.5 mmol/L. Weight-maintaining diets that included shakes with one of the dietary oil blends were provided during each of the five 30-day dietary phases. Dietary phases were separated by four-week washout periods. Treatment oils were canola oil, high oleic canola oil, high oleic canola oil enriched with docosahexaenoic acid (DHA), flax oil and safflower oil blend, and corn oil and safflower oil blend. A per protocol approach with a mixed model analysis was decided to be appropriate for data analysis. Results One hundred and seventy volunteers were randomized and 130 completed the study with a dropout rate of 23.5%. The mean plasma total DHA concentrations, which were analyzed among all participants as a measure of adherence, increased by more than 100% in the DHAenriched phase, compared to other phases, demonstrating excellent dietary adherence. Conclusions Recruitment and retention strategies were effective in achieving a sufficient number of participants who completed the study protocol to enable sufficient statistical power to resolve small differences in outcome measures. It is expected that the study will generate important data thereby enhancing our understanding of the effects of n-3, n-6, and n-9 fatty acidcontaining oils on CVD risks. [ABSTRACT FROM AUTHOR]

Abstract: In septic shock patients, alterations of plasma phospholipid fatty acid profile have never been described. The purpose of this monocentric, non-interventional, observational prospective study was to describe this fatty acid profile in the early phase of septic shock in intensive care unit. Thirty-seven adult patients with septic shock were included after the first day of stay in intensive care unit, before any form of artificial nutritional support. Plasma phospholipid fatty acid composition was determined by gas chromatography. All biological data from patients with septic shock were compared with laboratory reference values. Patients presented hypocholesterolemia and hypertriglyceridemia. They had low concentrations of phospholipid fatty acids specifically n-6 and n-3 polyunsaturated fatty acids (PUFAs) with a high n-6/n-3 ratio. Plasma phospholipid PUFA concentrations were strongly correlated with cholesterolemia. PUFAs/SFAs (saturated fatty acids) and PUFAs/MUFAs (monounsaturated fatty acids) ratios were low because of low percentage of n-6 and n-3 PUFAs and high percentage of SFAs and MUFAs. Low levels of plasma long chain PUFAs (≥20 carbons) were significantly associated with mortality at 28th day. In conclusion, plasma phospholipid FA profile of septic patients is very characteristic, close to that of acute respiratory distress syndrome and mortality is associated with long chain PUFA decrease. This profile could be explained by numerous non-exclusive physio-pathological processes 1) an activation of hepatic de novo lipogenesis that could contribute to hepatic steatosis, 2) an elevated adipose tissue lipolysis, 3) an increased free radical attack of FA by oxidative stress, 4) an over-production of inflammatory lipid mediators. [Copyright &y& Elsevier]

The fruit juice industry generates pomace as a valuable by-product especially rich in polyphenols, dietary fibers, vitamins, minerals, and unsaturated fatty acids. In the cookies used in this study, 30% of the gluten-free flour was replaced with dried and ground blueberry and raspberry pomace, rich source of polyphenols, dietary fibers, linoleic and alpha-linolenic acid. In order to examine whether the addition of blueberry and raspberry pomace in cookie formulation can have beneficial effects on certain blood parameters and anthropometric measurements, the designed cookies were tested in 20 healthy, normally fed female subjects, aged 30-50 years (41.35 ± 8.58 years) over four-week dietetic intervention study. Significant changes in the composition of fatty acids serum phospholipids, decrease in LDL-cholesterol level (20.16%), increase in adiponectin level (25.52%) and decrease in ALT and AST values were observed, thus indicating that inclusion of cookies containing blueberry and raspberry dried and ground pomace to usual diet might have positive effects on certain cardiovascular risk factors and liver function indicators., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Popović, Šarić, Martačić, Arsić, Jovanov, Stokić, Mišan and Mandić.)

Simple Summary: An association between increased metabolic demands and reduced dry matter intake is observed from late gestation to early lactation in donkeys. Furthermore, little is known about the nutritional and energy requirements of this period in animals. Changes in energy metabolism make donkeys more susceptible to metabolic diseases such as hyperlipemia, which is characterized by the mobilization of fatty acids from adipose tissue. A better knowledge of this period could improve animal husbandry, well-being, and health. The aim of this study was to analyze the plasma total lipid fraction, to highlight metabolic changes from the pre-foaling to post-foaling periods, using the gas chromatography technique. Our findings reveal a greater risk of metabolic disease in late gestation to early lactation in donkeys. The period from late gestation to early lactation is characterized by changes in energy metabolism. The aim of the current study was to analyze the plasma total lipid fraction using gas chromatography (GC) analysis, in order to highlight metabolic changes from the pre-foaling to post-foaling periods. Eleven pluriparous dairy jennies (mean age of 11.88 ± 3.79 years) belonging to the Amiata donkey breed were enrolled. Blood sampling was performed at 15 days before foaling (T0), and 15 (T1), 30 (T2), 60 (T3), and 90 (T4) days after foaling, for biochemical and GC analysis. A total of 37 fatty acids were identified in plasma samples: 4 medium chain (MCFA), 24 long chain (LCFA), and 9 very-long chain (VLCFA) fatty acids. Among them, 20 fatty acids changed significantly, and two fatty acid showed a trend toward significance. Furthermore, the LCFA, saturated, unsaturated, monounsaturated, and polyunsaturated ω-3 fatty acids changed significantly during the study period. The main alterations were between T0 and the other time points and appeared to be related to lipid metabolism, cellular structure and function, and inflammatory and immune responses. Our findings reveal greater energy requirements at the end of gestation compared to early lactation in donkeys. [ABSTRACT FROM AUTHOR]

The scope of this study was to assess the impact of calcium and conjugated linoleic acid (CLA) supplementation on plasma fatty acid profiles and to evaluate potential synergistic effects of both compounds against dietary obesity. Mice separated into five experimental groups were followed: control (C), high-fat diet (HF), HF with calcium (Ca), HF plus CLA and HF with both Ca and CLA. Plasma metabolites and fatty acids were determined by commercial kits and gas chromatography, respectively. Both dietary calcium and CLA supplementation contributed to lower body fat gain under a HF diet. Maximum efficacy was seen with calcium; no additional effect was associated with the combined treatment with CLA. Plasma leptin, adiponectin and HOMA index were in accordance with an altered glucose/insulin homeostasis in the HF and HF + CLA groups, whereas control levels were attained under Ca-enriched diets. Plasma fatty acids showed minor changes associated to CLA treatment, but a high impact on PUFA was observed under Ca-enriched diets. Our results show that the mechanism underlying the anti-obesity effects of calcium supplementation is mediated mainly by changes in PUFA plasma profile. In addition, the lack of synergy on body weight reduction in combination with associated lipid profiles of calcium and CLA suggests that calcium may interfere with absorption and/or bioactivity of CLA, which can be of relevance when using CLA-fortified dairy products against human obesity. [ABSTRACT FROM AUTHOR]

Abstract: Low plasma concentrations of docosahexaenoic acid (DHA) are reported in unsupplemented cystic fibrosis (CF) patients. Forty-one CF patients aged from 6 to 12 years were randomized to receive high-dose DHA (100mg/kg/day in the first month and 1g per day thereafter through a 12-month supplementation) or placebo (germ oil). Primary outcome was percentage change in plasma AA:DHA ratio. Secondary outcomes were changes in the number of pulmonary exacerbations compared to previous year, lung function, BMI, skinfold thicknesses, and body composition assessed by DXA and in serum concentrations of C-reactive protein, cytokines and vitamin (α-tocopherol and retinol). Compared to the control group plasma AA:DHA ratio decreased in the intervention group after 6 months (median percentage changes: −73% in the intervention group vs. −10% in the control group, P=0.001). No differences were detected between groups for secondary outcomes. Despite a decrease of the AA/DHA ratio, DHA supplementation for one year did not induce any significant biochemical and clinical improvement in CF patients. [Copyright &y& Elsevier]

The aim of this study was to assess baseline levels and changes in plasma fatty acid profiles in children and adolescents with ADHD, in a placebo-controlled study with Omega 3/6 supplementation, and to compare with treatment response. Seventy-five children and adolescents aged 8-18 years with DSM-IV ADHD were randomized to 3 months of Omega 3/6 (Equazen eye q) or placebo, followed by 3 months of open phase Omega 3/6 for all. n-3, n-6, n-6/n-3 ratio, EPA and DHA in plasma were measured at baseline, 3 and 6 months. Subjects with more than 25 % reduction in ADHD symptoms were classified as responders. At baseline, no significant differences in mean fatty acid levels were seen across active/placebo groups or responder/non-responder groups. The 0-3 month changes in all parameters were significantly greater in the active group ( p < 0.01). Compared to non-responders, the 6-month responders had significantly greater n-3 increase at 3 months and decrease in n-6/n-3 ratio at 3 and 6 months ( p < 0.05). Omega 3/6 supplementation had a clear impact on fatty acid composition of plasma phosphatidyl choline in active versus placebo group, and the fatty acid changes appear to be associated with treatment response. The most pronounced and long-lasting changes for treatment responders compared to non-responders were in the n-6/n-3 ratio. [ABSTRACT FROM AUTHOR]

As the consumption of fructose and saturated fatty acids (FAs) has greatly increased in western diets and is linked with an increased risk of metabolic syndrome, the aim of this study was to investigate the effects of a moderate (10 weeks) and a prolonged (30 weeks) high fructose and saturated fatty acid (HFS) diet on plasma FA composition in rats. The effects of a few weeks of HFS diet had already been described, but in this paper we tried to establish whether these effects persist or if they are modified after 10 or 30 weeks. We hypothesized that the plasma FA profile would be altered between 10 and 30 weeks of the HFS diet. Rats fed with either the HFS or a standard diet were tested after 10 weeks and again after 30 weeks. After 10 weeks of feeding, HFS-fed rats developed the metabolic syndrome, as manifested by an increase in fasting insulinemia, total cholesterol and triglyceride levels, as well as by impaired glucose tolerance. Furthermore, the plasma FA profile of the HFS group showed higher proportions of monounsaturated FAs like palmitoleic acid [16:1( n-7)] and oleic acid [18:1( n-9)], whereas the proportions of some polyunsaturated n-6 FAs, such as linoleic acid [18:2( n-6)] and arachidonic acid [20:4( n-6)], were lower than those in the control group. After 30 weeks of the HFS diet, we observed changes mainly in the levels of 16:1( n-7) (decreased) and 20:4( n-6) (increased). Together, our results suggest that an HFS diet could lead to an adaptive response of the plasma FA profile over time, in association with the development of the metabolic syndrome. [ABSTRACT FROM AUTHOR]