Differences in Plasma Fatty Acid Composition Related to Chronic Pancreatitis: A Pilot Study.

OBJECTIVES: Chronic pancreatitis (CP) is an inflammatory disease affecting the absorption of fat-soluble nutrients. Signaling in pancreatic cells that lead to inflammation may be influenced by fatty acids (FAs) through diet and de novo lipogenesis. Here, we investigated the relationship between plasma FA composition in CP with heterogeneity of etiology and complications of CP. MATERIALS AND METHODS: Blood and clinical parameters were collected from subjects with CP (n = 47) and controls (n = 22). Plasma was analyzed for FA composition using gas chromatography and compared between controls and CP and within CP. RESULTS: Palmitic acid increased, and linoleic acid decreased in CP compared with controls. Correlations between age or body mass index and FAs are altered in CP compared with controls. Diabetes, pancreatic calcifications, and substance usage, but not exocrine pancreatic dysfunction, were associated with differences in oleic acid and linoleic acid relative abundance in CP. De novo lipogenesis index was increased in the plasma of subjects with CP compared with controls and in calcific CP compared with noncalcific CP. CONCLUSIONS: Fatty acids that are markers of de novo lipogenesis and linoleic acid are dysregulated in CP depending on the etiology or complication. These results enhance our understanding of CP and highlight potential pathways targeting FAs for treating CP.

Restricted carbohydrate diets below 45% energy are not associated with risk of mortality in the National Health and Nutrition Examination Survey, 1999-2018.

Introduction: Cardiometabolic diseases (CMD) are the leading causes of death for people living in the United States. Dietary strategies, such as restricting carbohydrate intake, are becoming popular strategies for improving health status. However, there is limited and often contradictory evidence on whether restricting carbohydrate intake is related to all-cause, CMD, or cardiovascular disease (CVD) mortality. Methods: The objective of the present study was to evaluate the association between restricted carbohydrate diets (<45%en) and mortality from all-causes, CMD, and CVD, stratified by fat amount and class. Data were acquired using the National Health and Nutrition Examination Survey (1999-2018) linked with mortality follow-up until December 31, 2019 from the Public-use Linked Mortality Files. Multivariable survey-weighted Cox proportional hazards models estimated hazard ratios for 7,958 adults (≥20 y) that consumed <45%en from carbohydrates and 27,930 adults that consumed 45-65%en from carbohydrates. Results: During the study period a total of 3,780 deaths occurred, including 1,048 from CMD and 1,007 from CVD, during a mean follow-up of 10.2 y. Compared to individuals that met carbohydrate recommendations (45-65%en), those that consumed carbohydrate restricted diets (<45%en) did not have significantly altered risk of mortality from all-causes (HR: 0.98; 95% CI: 0.87, 1.11), CMD (1.18; 0.95, 1.46), or CVD (1.20; 0.96, 1.49). These findings were maintained when the restricted carbohydrate diet group was stratified by intake of total fat, saturated fat (SFA), monounsaturated fat (MUFA), and polyunsaturated fat (PUFA). Discussion: Carbohydrate restriction (<45%en) was not associated with mortality from all-causes, CVD, or CMD. Greater efforts are needed to characterize the risk of mortality associated with varied degrees of carbohydrate restriction, e.g., low (<26%en) and high (>65%en) carbohydrate diets separately.

Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations in Chronic Pancreatitis: A Multicenter, Cross-Sectional Study.

INTRODUCTION: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations. METHODS: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear cells (PBMCs) from controls (n = 16), AP/RAP (n = 17), and CP (n = 15) were measured by cytometry by time-of-flight. RESULTS: Plasma NGAL was elevated in subjects with CP compared with controls (area under the curve [AUC] = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, body mass index, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared with CP without diabetes ( P < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower, whereas dihomo-γ-linolenic and adrenic acids were elevated in CP ( P < 0.05). Linoleic acid was elevated in CP with diabetes compared with CP subjects without diabetes ( P = 0.0471). DISCUSSION: Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.

Gut Microbiota Richness and Diversity Track With T Cell Aging in Healthy Adults.

BACKGROUND: This study examined how gut microbiota diversity and richness relate to T cell aging among 96 healthy adults of all ages. It also explored whether these links differed throughout the lifespan. METHODS: Peripheral blood was obtained from 96 study participants (N = 96, aged 21-72) to assess mRNA markers of T cell aging (p16ink4a, p14ARF, B3gat1, Klrg1) and DNA methylation. T cell aging mRNA markers were combined into an aging index, and the Horvath epigenetic clock algorithm was used to calculate epigenetic age based on DNA methylation status of over 500 loci. Participants also collected a stool sample from which the V4 region of the 16S rRNA gene was sequenced to derive the Shannon and Simpson diversity indices, and the total count of observed operational taxonomic units (richness). Models controlled for BMI, comorbidities, sex, dietary quality, smoking status, physical activity, and sleep quality. RESULTS: Lower microbiota richness was associated with higher T cell age based on mRNA markers, but when probing the region of significance, this relationship was only significant among adults 45 years and older (p = .03). Lower Shannon diversity (p = .05) and richness (p = .07) marginally correlated with higher epigenetic age (ie, greater T cell DNA methylation). CONCLUSIONS: Gut microbiota complexity may correspond with the rate of T cell aging, especially in mid-to-late life. These results suggest an interplay between the gut microbiome and immunological aging that warrants further experimental work.

Consuming a Linoleate-Rich Diet Increases Concentrations of Tetralinoleoyl Cardiolipin in Mouse Liver and Alters Hepatic Mitochondrial Respiration.

BACKGROUND: Hepatic mitochondrial dysfunction is a major cause of fat accumulation in the liver. Individuals with fatty liver conditions have hepatic mitochondrial structural abnormalities and a switch in the side chain composition of the mitochondrial phospholipid, cardiolipin, from poly- to monounsaturated fatty acids. Linoleic acid (LA), an essential dietary fatty acid, is required to remodel nascent cardiolipin (CL) to its tetralinoleoyl cardiolipin (L4CL, CL with 4 LA side chains) form, which is integral for mitochondrial membrane structure and function to promote fatty acid oxidation. It is unknown, however, whether increasing LA in the diet can increase hepatic L4CL concentrations and improve mitochondrial respiration in the liver compared with a diet rich in monounsaturated and saturated fatty acids. OBJECTIVES: The main aim of this study was to test the ability of a diet fortified with LA-rich safflower oil (SO), compared with the one fortified with lard (LD), to increase concentrations of L4CL and improve mitochondrial respiration in the livers of mice. METHODS: Twenty-four (9-wk-old) C57 BL/J6 male mice were fed either the SO or LD diets for ∼100 d, whereas food intake and body weight, fasting glucose, and glucose tolerance tests were performed to determine any changes in glycemic control. RESULTS: Livers from mice fed SO diet had higher relative concentrations of hepatic L4CL species compared with LD diet-fed mice (P value = 0.004). Uncoupled mitochondria of mice fed the SO diet, compared with LD diet, had an increased baseline oxygen consumption rate (OCR) and succinate-driven respiration (P values = 0.03 and 0.01). SO diet-fed mice had increased LA content in all phospholipid classes compared with LD-fed mice (P < 0.05). CONCLUSIONS: Our findings reveal that maintaining or increasing hepatic L4CL may result in increased OCR in uncoupled hepatic mitochondria in healthy mice whereas higher oleate content of CL reduced mitochondrial function shown by lower OCR in uncoupled mitochondria.

Potential Neuroprotective Effects of Dietary Omega-3 Fatty Acids on Stress in Alzheimer's Disease.

BACKGROUND: A large number of individual potentially modifiable factors are associated with risk for Alzheimer's disease (AD). However, less is known about the interactions between the individual factors. METHODS: In order to begin to examine the relationship between a pair of factors, we performed a pilot study, surveying patients with AD and controls for stress exposure and dietary omega-3 fatty acid intake to explore their relationship for risk of AD. RESULTS: For individuals with the greatest stress exposure, omega-3 fatty acid intake was significantly greater in healthy controls than in AD patients. There was no difference among those with low stress exposure. CONCLUSIONS: These initial results begin to suggest that omega-3 fatty acids may mitigate AD risk in the setting of greater stress exposure. This will need to be examined with larger populations and other pairs of risk factors to better understand these important relationships. Examining how individual risk factors interact will ultimately be important for learning how to optimally decrease the risk of AD.

Omega-3 fatty acids reduce depressive symptoms only among the socially stressed: A corollary of the social signal transduction theory of depression.

OBJECTIVE: There is mixed evidence about whether omega-3 fatty acids reduce depressive symptoms. We previously reported that 4 months of omega-3 supplementation reduced inflammatory responsivity to a lab-based social stressor. In another study, we showed that those with exaggerated inflammatory responsivity to a social stressor had the greatest depressive symptom increases over time, especially if they experienced frequent social stress. Here we tested whether omega-3 supplementation reduced subthreshold depressive symptoms among those who experienced frequent social stress. METHOD: Healthy, sedentary, generally overweight middle-aged and older adults (N = 138) were randomly assigned to 4 months of pill placebo (n = 46), 1.25 grams per day (g/d) omega-3 (n = 46), or 2.5 g/d omega-3 (n = 46). At a baseline visit and monthly follow-up visits, they reported depressive symptoms and had their blood drawn to assess plasma levels of omega-3 fatty acids. Participants completed the Trier Inventory of Chronic Stress at Visit 2 and the Test of Negative Social Exchange at Visit 3. RESULTS: Among those who were overweight or obese, both doses of omega-3 reduced depressive symptoms only in the context of frequent hostile interactions and social tension, and 2.5 g/d of omega-3 lowered depressive symptoms among those with less social recognition or more performance pressure (ps < .05). Findings were largely corroborated with plasma omega-3 fatty acids. No other social stress or work stress measure moderated omega-3 fatty acids' relationship with depressive symptoms (ps > .05). CONCLUSIONS: Omega-3 fatty acids' antidepressant effect may be most evident among those who experience frequent social stress, perhaps because omega-3 fatty acids reduce inflammatory reactivity to social stressors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Fat Intake Modifies the Association between Restricted Carbohydrate Diets and Prevalent Cardiometabolic Diseases among Adults in the United States: National Health and Nutrition Examination Survey, 1999-2018.

Background: Cardiometabolic diseases (CMDs), which include heart disease, stroke, and diabetes, account for over one-third of the mortality burden in the United States annually. Nearly one-half of all deaths from CMD are attributable to suboptimal diet quality, and many Americans are turning to special diets for general health improvement. Among the most popular of these diets restrict daily carbohydrate intake to <45% of energy, yet their association with CMD is not well understood. Objectives: This study evaluated the association between restricted carbohydrate diets and prevalent CMD, stratified by fat intake. Methods: Dietary and CMD data were retrieved from 19,078 participants aged ≥20 y in the National Health and Nutrition Examination Survey, 1999-2018. The National Cancer Institute methodology was used to assess usual dietary intake. Results: Compared to participants that met recommendations for all macronutrients, those that consumed restricted carbohydrate diets were 1.15 (95% CI: 1.14, 1.16) times as likely to have CMD; and those that met recommendations for carbohydrates, but not all macronutrients, were 1.02 (95% CI: 1.02, 1.03) times as likely to have CMD. Higher intakes of saturated and polyunsaturated fat were associated with greater prevalence of CMD in restricted and recommended carbohydrate intake groups. Higher intake of monounsaturated fat was associated with lower prevalence of CMD among participants that met carbohydrate, but not all macronutrient, recommendations. Conclusions: To our knowledge, this is the first nationally representative study to evaluate the relationship between carbohydrate restriction and CMD, stratifying by fat intake. Greater efforts are needed to understand longitudinal relationships between carbohydrate restriction and CMD.

Association between skeletal muscle mitochondrial dysfunction and insulin resistance in patients with rheumatoid arthritis: a case-control study.

BACKGROUND: Insulin resistance affects a substantial proportion of patients with rheumatoid arthritis (RA). Skeletal muscle mitochondrial dysfunction results in the accumulation of lipid intermediates that interfere with insulin signaling. We therefore sought to determine if lower oxidative phosphorylation and muscle mitochondrial content are associated with insulin resistance in patients with RA. METHODS: This was a cross-sectional prospective study of RA patients. Matsuda index from the glucose tolerance test was used to estimate insulin sensitivity. Mitochondrial content was measured by citrate synthase (CS) activity in snap-frozen muscle samples. Mitochondrial function was measured by using high-resolution respirometry of permeabilized muscle fibers and electron transport chain complex IV enzyme kinetics in isolated mitochondrial subpopulations. RESULTS: RA participants demonstrated lower insulin sensitivity as measured by the Matsuda index compared to controls [median 3.95 IQR (2.33, 5.64) vs. 7.17 (5.83, 7.75), p = 0.02]. There was lower muscle mitochondrial content among RA vs. controls [median 60 mU/mg IQR (45, 80) vs. 79 mU/mg (65, 97), p = 0.03]. Notably, OxPhos normalized to mitochondrial content was higher among RA vs. controls [mean difference (95% CI) = 0.14 (0.02, 0.26), p = 0.03], indicating a possible compensatory mechanism for lower mitochondrial content or lipid overload. Among RA participants, the activity of muscle CS activity was not correlated with the Matsuda index (ρ = - 0.05, p = 0.84), but it was positively correlated with self-reported (IPAQ) total MET-minutes/week (ρ = 0.44, p = 0.03) and Actigraph-measured time on physical activity (MET rate) (ρ = 0.47, p = 0.03). CONCLUSIONS: Mitochondrial content and function were not associated with insulin sensitivity among participants with RA. However, our study demonstrates a significant association between muscle mitochondrial content and physical activity level, highlighting the potential for future exercise interventions that enhance mitochondrial efficiency in RA patients.

Greenhouse gas emissions, cost, and diet quality of specific diet patterns in the United States.

BACKGROUND: Major policy agendas are calling for accelerated investment in research that addresses the impact of diet patterns on multiple domains of sustainability. OBJECTIVES: To evaluate the comparative greenhouse gas emissions, diet cost, and diet quality of plant-based, low-grain, restricted carbohydrate, low-fat, and time-restricted diet patterns on a daily per capita basis. METHODS: Dietary data from the National Health and Nutrition Examination Survey (2013-2016, n = 4025) were merged with data on greenhouse gas emissions (GHGEs) and food prices from multiple databases. The Healthy Eating Index-2015 was used to measure diet quality. RESULTS: The plant-based diet pattern had the lowest GHGEs [3.5 kg carbon dioxide equivalent (CO2eq); 95% confidence interval (CI): 3.3, 3.8 kg CO2eq] and among the lowest diet cost ($11.51; 95% CI: $10.67, $12.41), but diet quality (45.8; 95% CI: 43.3, 48.5) was similar (P > 0.005) to most other diet patterns. All of the sustainability impacts of the low-grain diet pattern were intermediate. The restricted carbohydrate diet pattern had the highest diet cost ($18.46; 95% CI: $17.80, $19.13) but intermediate diet quality (46.8; 95% CI: 45.7, 47.9) and moderate-to-high GHGEs (5.7 kg CO2eq; 95% CI: 5.4, 5.9 kg CO2eq). The low-fat diet pattern had the highest diet quality (52.0; 95% CI: 50.8, 53.1) and intermediate GHGEs (4.4 kg CO2eq; 95% CI: 4.1, 4.6 kg CO2eq) and diet cost ($14.53; 95% CI: $13.73, $15.38). The time-restricted diet pattern had among the lowest diet quality score (42.6; 95% CI: 40.8, 44.6), had GHGEs similar to most other diet patterns (4.6 kg CO2eq; 95% CI: 4.2, 5.0 kg CO2eq), and low-to-moderate diet cost ($12.34; 95% CI: $11.38, $13.40). CONCLUSIONS: Most diet patterns are associated with sustainability trade-offs. The nature of these trade-offs can help inform discussions on food and nutrition policy in the United States, including the National Strategy on Hunger, Nutrition, and Health, and future Dietary Guidelines for Americans.

Changes in Plasma Fatty Acid Abundance Related to Chronic Pancreatitis: A Pilot Study.

Objectives: Chronic pancreatitis (CP) is an inflammatory disease that affects the absorption of nutrients like fats. Molecular signaling in pancreatic cells can be influenced by fatty acids (FAs) and changes in FA abundance could impact CP-associated complications. Here, we investigated FA abundance in CP compared to controls and explored how CP-associated complications and risk factors affect FA abundance. Methods: Blood and clinical parameters were collected from subjects with (n=47) and without CP (n=22). Plasma was analyzed for relative FA abundance using gas chromatography and compared between controls and CP. Changes in FA abundance due to clinical parameters were also assessed in both groups. Results: Decreased relative abundance of polyunsaturated fatty acids (PUFAs) and increased monounsaturated fatty acids (MUFAs) were observed in subjects with CP in a sex-dependent manner. The relative abundance of linoleic acid increased, and oleic acid decreased in CP subjects with exocrine pancreatic dysfunction and a history of substance abuse. Conclusions: Plasma FAs like linoleic acid are dysregulated in CP in a sex-dependent manner. Additionally, risk factors and metabolic dysfunction further dysregulate FA abundance in CP. These results enhance our understanding of CP and highlight potential novel targets and metabolism-related pathways for treating CP.

Consumption of Key Food Groups by Individuals Consuming Popular Diet Patterns: Mixed Effects of Replacing Foods High in Added Sugar, Sodium, Saturated Fat, and Refined Grains.

Adults in the United States are increasingly following 'popular' diet patterns that restrict food groups, macronutrients, or eating time. However, the intake of food groups associated with these diet patterns has not been well characterized. The objectives of this study were to (1) characterize the mean intake of food groups among consumers of popular diet patterns in the US, and (2) model the effect of targeted food substitutions on the intake of food groups. Data were acquired from the National Health and Nutrition Examination Survey, 2005-2018 (n = 34,411). A diet model was developed to assess the effects of replacing one serving each of foods highest in added sugar, sodium, saturated fat, and refined grains with healthy alternatives on the intake of key food groups for each diet pattern. Modeled replacement resulted in increased intake of fruit and whole grains and decreased intake of dairy for most diet patterns, while the effects on the intake of vegetables, protein foods, and oils were variable across diet patterns. The complexity of the natural eating environment, in which many people consume mixed dishes that include both healthy and less healthy ingredients, produces a challenge for health professionals when providing dietary counseling. Nevertheless, this substitution approach may help improve adherence to dietary guidelines, especially if used as a steppingstone for further dietary improvement.

Potential Cardioprotective Effects and Lipid Mediator Differences in Long-Chain Omega-3 Polyunsaturated Fatty Acid Supplemented Mice Given Chemotherapy.

Many commonly used chemotherapies induce mitochondrial dysfunction in cardiac muscle, which leads to cardiotoxicity and heart failure later in life. Dietary long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) have demonstrated cardioprotective function in non-chemotherapy models of heart failure, potentially through the formation of LC n-3 PUFA-derived bioactive lipid metabolites. However, it is unknown whether dietary supplementation with LC n-3 PUFA can protect against chemotherapy-induced cardiotoxicity. To test this, 36 female ovariectomized C57BL/6J mice were randomized in a two-by-two factorial design to either a low (0 g/kg EPA + DHA) or high (12.2 g/kg EPA + DHA) LC n-3 PUFA diet, and received either two vehicle or two chemotherapy (9 mg/kg anthracycline + 90 mg/kg cyclophosphamide) tail vein injections separated by two weeks. Body weight and food intake were measured as well as heart gene expression and fatty acid composition. Heart mitochondria were isolated using differential centrifugation. Mitochondrial isolate oxylipin and N-acylethanolamide levels were measured by mass spectrometry after alkaline hydrolysis. LC n-3 PUFA supplementation attenuated some chemotherapy-induced differences (Myh7, Col3a1) in heart gene expression, and significantly altered various lipid species in cardiac mitochondrial preparations including several epoxy fatty acids [17(18)-EpETE] and N-acylethanolamines (arachidonoylethanolamine, AEA), suggesting a possible functional link between heart lipids and cardiotoxicity.

Quality of Popular Diet Patterns in the United States: Evaluating the Effect of Substitutions for Foods High in Added Sugar, Sodium, Saturated Fat, and Refined Grains.

Background: Many Americans have adopted popular diet patterns for general health improvement that restrict specific foods, macronutrients, or eating time. However, there is limited evidence to characterize the quality of these diet patterns. Objectives: This study 1) evaluated the quality of popular diet patterns in the United States and 2) modeled the effect of targeted food substitutions on diet quality. Methods: Dietary data from 34,411 adults ≥20 y old were acquired from the NHANES, 2005-2018. Dietary intake was assessed using the National Cancer Institute's usual intake methodology, and the Healthy Eating Index-2015 was used to evaluate diet quality. A diet model was used to evaluate the effect of targeted food substitutions on diet quality. Results: A pescatarian diet pattern had the highest diet quality (65.2; 95% CI: 64.0, 66.4), followed by vegetarian (63.0; 95% CI: 62.0, 64.0), low-grain (62.0; 95% CI: 61.6, 62.4), restricted-carbohydrate (56.9; 95% CI: 56.6, 57.3), time-restricted (55.2; 95% CI: 54.8, 55.5), and high-protein (51.8; 95% CI: 51.0, 62.7) diet patterns. Modeled replacement of ≤3 daily servings of foods highest in added sugar, sodium, saturated fat, and refined grains with alternative foods led to an increase in diet quality and a decrease in energy intake for most diet patterns. Conclusions: Low diet quality was observed for all popular diet patterns evaluated in this study. Modeled dietary shifts that align with recommendations to choose foods lower in added sugar, sodium, saturated fat, and refined grains led to modest improvements in diet quality and larger reductions of energy intake. Greater efforts are needed to encourage the adoption of dietary patterns that emphasize consumption of a variety of high-quality food groups.

Linoleate-Rich Safflower Oil Diet Increases Linoleate-Derived Bioactive Lipid Mediators in Plasma, and Brown and White Adipose Depots of Healthy Mice.

Polyunsaturated fats are energy substrates and precursors to the biosynthesis of lipid mediators of cellular processes. Adipose tissue not only provides energy storage, but influences whole-body energy metabolism through endocrine functions. How diet influences adipose-lipid mediator balance may have broad impacts on energy metabolism. To determine how dietary lipid sources modulate brown and white adipose tissue and plasma lipid mediators, mice were fed low-fat (15% kcal fat) isocaloric diets, containing either palm oil (POLF) or linoleate-rich safflower oil (SOLF). Baseline and post body weight, adiposity, and 2-week and post fasting blood glucose were measured and lipid mediators were profiled in plasma, and inguinal white and interscapular brown adipose tissues. We identified over 30 species of altered lipid mediators between diets and found that these changes were unique to each tissue. We identified changes to lipid mediators with known functional roles in the regulation of adipose tissue expansion and function, and found that there was a relationship between the average fold difference in lipid mediators between brown adipose tissue and plasma in mice consuming the SOLF diet. Our findings emphasize that even with a low-fat diet, dietary fat quality has a profound effect on lipid mediator profiles in adipose tissues and plasma.

Linoleic Acid-Rich Oil Alters Circulating Cardiolipin Species and Fatty Acid Composition in Adults: A Randomized Controlled Trial.

SCOPE: Higher circulating linoleic acid (LA) and muscle-derived tetralinoleoyl-cardiolipin (LA4 CL) are each associated with decreased cardiometabolic disease risk. Mitochondrial dysfunction occurs with low LA4 CL. Whether LA-rich oil fortification can increase LA4 CL in humans is unknown. The aims of this study are to determine whether dietary fortification with LA-rich oil for 2 weeks increases: 1) LA in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC); and 2) LA4 CL in PBMC in adults. METHODS AND RESULTS: In this randomized controlled trial, adults are instructed to consume one cookie per day delivering 10 g grapeseed (LA-cookie, N = 42) or high oleate (OA) safflower (OA-cookie, N = 42) oil. In the LA-cookie group, LA increases in plasma, erythrocyte, and PBMC by 6%, 7%, and 10% respectively. PBMC and erythrocyte OA increase by 7% and 4% in the OA-cookie group but is unchanged in the plasma. PBMC LA4 CL increases (5%) while LA3 OA1 CL decreases (7%) in the LA-cookie group but are unaltered in the OA-cookie group. CONCLUSIONS: LA-rich oil fortification increases while OA-oil has no effect on LA4 CL in adults. Because LA-rich oil fortification reduces cardiometabolic disease risk and increases LA4 CL, determining whether mitochondrial dysfunction is repaired through dietary fortification is warranted.

Perceived social support predicts self-reported and objective health and health behaviors among pregnant women.

Perinatal health and health behaviors play a crucial role in maternal and neonatal health. Data examining psychosocial factors which predict self-reported health and health behaviors as well as objective indicators downstream of health behaviors among pregnant women are lacking. In this longitudinal study design with 131 pregnant women, perceived social support was examined as a predictor of self-rated health and average levels of sleep quality, health-promoting and health-impairing behaviors, and red blood cell (RBC) polyunsaturated fatty acids across early, mid, and late pregnancy. Participants provided a blood sample and fatty acid methyl esters were analyzed by gas chromatography. Measures included the Multidimensional Scale of Perceived Social Support, Pittsburgh Sleep Quality Index, and Prenatal Health Behavior Scale. Regression models demonstrated that, after adjustment for income, race/ethnicity, age, relationship status, pre-pregnancy body mass index, greater social support was associated with better self-rated health (p = 0.001), greater sleep quality (p = 0.001), fewer health-impairing behaviors (p = 0.02), and higher RBC omega-3 fatty acids (p = 0.003). Associations among social support with health-promoting behaviors, RBC omega-6 fatty acids, or gestational weight gain were not significant. Findings underscore the benefits of perceived social support in the context of pregnancy. Examination of pathways that link social support with these outcomes will be meaningful in determining the ways in which perinatal psychosocial interventions may promote health.

Linoleic Acid Intake and Physical Function: Pilot Results from the Health ABC Energy Expenditure Sub-Study.

Background: Dietary fat quality is important for health and physical functioning in older adults. Linoleic acid is a dietary polyunsaturated fatty acid that is necessary for optimal inner-mitochondrial membrane function. However, limited evidence exists for examining the role of linoleic acid intake on indices of mobility and physical function. In this pilot study, we sought to examine the associations between linoleic acid intake and physical functioning in older adults. Methods: This secondary analysis of data from the Health, Aging, and Body Composition energy expenditure sub-study was conducted for our investigation. Ability to complete physical tasks such as climbing a flight of stairs, walking a quarter mile, and lifting 10 lbs. was self-reported. Daily linoleic acid intake was estimated from a food frequency questionnaire. Persons with daily linoleic acid intake below approximately 85% of Adequate Intake were considered as having low linoleic acid intake. Covariate-adjusted logistic models were used for the analyses. Results: The final analytical sample included 317 participants aged 74.4 ± 2.8 years who consumed 18.9 ± 11.4 g/day of linoleic acid, with 78 (24.6%) participants having low daily linoleic acid intake. Persons with low daily linoleic acid intake had 2.58 (95% confidence interval: 1.27-5.24) greater odds for a limitation in climbing stairs. Conclusions: Our pilot investigation found that low daily linoleic acid intake could be associated with physical function in older adults. Dietitians working with older patients may want to consider the importance of daily linoleic acid intake for health and certain physical function tasks.

Altered Plasma Fatty Acid Abundance Is Associated with Cachexia in Treatment-Naïve Pancreatic Cancer.

Cachexia occurs in up to 80% of pancreatic ductal adenocarcinoma (PDAC) patients and is characterized by unintentional weight loss and tissue wasting. To understand the metabolic changes that occur in PDAC-associated cachexia, we compared the abundance of plasma fatty acids (FAs), measured by gas chromatography, of subjects with treatment-naïve metastatic PDAC with or without cachexia, defined as a loss of > 2% weight and evidence of sarcopenia (n = 43). The abundance of saturated, monounsaturated, and polyunsaturated FAs was not different between subjects with cachexia and those without. Oleic acid was significantly higher in subjects with cachexia (p = 0.0007) and diabetes (p = 0.015). Lauric (r = 0.592, p = 0.0096) and eicosapentaenoic (r = 0.564, p = 0.015) acids were positively correlated with age in cachexia patients. Subjects with diabetes (p = 0.021) or both diabetes and cachexia (p = 0.092) had low palmitic:oleic acid ratios. Linoleic acid was lower in subjects with diabetes (p = 0.018) and correlated with hemoglobin (r = 0.519, p = 0.033) and albumin (r = 0.577, p = 0.015) in subjects with cachexia. Oleic or linoleic acid may be useful treatment targets or biomarkers of cachexia in patients with metastatic PDAC, particularly those with diabetes.

Dietary omega-3 fatty acid intake impacts peripheral blood DNA methylation -anti-inflammatory effects and individual variability in a pilot study.

Omega-3 or n-3 polyunsaturated fatty acids (PUFAs) are widely studied for health benefits that may relate to anti-inflammatory activity. However, mechanisms mediating an anti-inflammatory response to n-3 PUFA intake are not fully understood. Of interest is the emerging role of fatty acids to impact DNA methylation (DNAm) and thereby modulate mediating inflammatory processes. In this pilot study, we investigated the impact of n-3 PUFA intake on DNAm in inflammation-related signaling pathways in peripheral blood mononuclear cells (PBMCs) of women at high risk of breast cancer. PBMCs of women at high risk of breast cancer (n=10) were obtained at baseline and after 6 months of n-3 PUFA (5 g/d EPA+DHA dose arm) intake in a previously reported dose finding trial. DNA methylation of PBMCs was assayed by reduced representation bisulfite sequencing (RRBS) to obtain genome-wide methylation profiles at the single nucleotide level. We examined the impact of n-3 PUFA on genome-wide DNAm and focused upon a set of candidate genes associated with inflammation signaling pathways and breast cancer. We identified 24,842 differentially methylated CpGs (DMCs) in gene promoters of 5507 genes showing significant enrichment for hypermethylation in both the candidate gene and genome-wide analyses. Pathway analysis identified significantly hypermethylated signaling networks after n-3 PUFA treatment, such as the Toll-like Receptor inflammatory pathway. The DNAm pattern in individuals and the response to n-3 PUFA intake are heterogeneous. PBMC DNAm profiling suggests a mechanism whereby n-3 PUFAs may impact inflammatory cascades associated with disease processes including carcinogenesis.