linoleic-acid and Cardiovascular-Diseases

As heart disease and type 2 diabetes mellitus (T2DM) cases continue to rise, identifying lifestyle modifications to prevent cardiometabolic disease (CMD) is urgently needed. Clinical evidence consistently shows that higher dietary or biomarker levels of linoleic acid (LA; 18:2n6) reduce metabolic syndrome (Mets) and reduce the risk for CMD. Yet, dietary recommendations to include LA as part of a lifestyle plan with the goal of preventing CMD remain elusive.. Clinical interventions consistently show that dietary the addition of LA to the diet improves body composition, dyslipidemia, and insulin sensitivity while reducing systemic inflammation and fatty liver. These effects of LA position dietary LA-rich oils as a potential dietary strategy to aid in preventing CMD. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that are cellular targets for many polyunsaturated fatty acids and oxylipin metabolites. PPAR activation can regulate dyslipidemia, insulin sensitivity, adipose biology, and inflammation, potentially explaining the plethora of effects of dietary LA on aspects of CMD.. Unraveling the cellular mechanism(s) of LA to impact PPAR activity may reset a false dogma that LA, as a member of the omega-6 fatty acid family, promotes inflammation in humans. In fact, LA appears to reduce inflammation and reduce risk for CMD.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fatty Acids, Omega-6; Humans; Inflammation; Insulin Resistance; Linoleic Acid; Peroxisome Proliferator-Activated Receptors

Polyunsaturated fatty acids (PUFAs) are long chain fatty acids that are characterized by the presence of more than one double bond. These include fatty acids such as ꞷ-3-α-linolenic acid (ALA) and ꞷ-6 -linoleic acid (LA) which can only be obtained from dietary sources and are therefore termed essential fatty acids. They contain the building blocks for dihomo-γ-linolenic acid and arachidonic acid in the ꞷ-6 family as well as eicosapentaenoic acid and docosahexaenoic acid in the ꞷ-3 family. Both ALA and LA are important constituents of animal and plant cell membranes and are important components of anti-inflammatory and pro-inflammatory hormones and therefore, often modulate cellular immunity under chronic inflammatory states. The variation in physiological PUFA levels is under significant genetic influence, the fatty acid desaturase (FADS) genes being key regulators of PUFA metabolism. These genetic variants have been shown to alter fatty acid metabolism and influence the onset and progression of various metabolic conditions. This detailed review discusses the role of PUFAs, diet and genotypes in risk for cardiovascular diseases.

Topics: alpha-Linolenic Acid; Animals; Cardiovascular Diseases; Diet; Fatty Acid Desaturases; Genotype; Humans; Inflammation; Linoleic Acid; Obesity; Polymorphism, Single Nucleotide; Risk Factors

This narrative review aims to discuss the more relevant evidence on the role of linoleic acid (LA), a n-6 essential fatty acid that constitutes the predominant proportion of dietary polyunsaturated fatty acids (PUFA), in cardiovascular health. Although LA can be metabolized into Arachidonic Acid (AA), a 20 carbon PUFA which is the precursor of eicosanoids, including some with proinflammatory or prothrombotic-vasoconstrictor action, the large majority of experimental and clinical studies have assessed the potential benefit of increasing dietary intake of LA. Overall, data from clinical studies and meta-analyses suggest an association between high dietary intakes or tissue levels of n-6 PUFA, and specifically LA, and the improvement of cardiovascular risk (mainly of the plasma lipid profile), as well as long-term glycaemic control and insulin resistance. Most observational data show that elevated/increased dietary intake or tissue levels of LA is associated with a reduced incidence of cardiovascular diseases (mainly coronary artery diseases) and of new onset metabolic syndrome or type 2 diabetes. The effects of LA (or n-6 PUFA) in other physio-pathological areas are less clear. High quality clinical trials are needed to assess both the actual amplitude and the underlying mechanisms of the health effects related to dietary intake of this essential fatty acid.

Topics: Cardiovascular Diseases; Diet; Humans; Linoleic Acid; Metabolic Diseases

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

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Fatty Acids, Omega-6; Female; Humans; Linoleic Acid; Male; Middle Aged; Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Young Adult

Cardiovascular disease (CVD) is the leading cause of death worldwide. Risk factors for developing this disease include high serum concentrations of total cholesterol, triglycerides, low-density lipoproteins, very-low density lipoproteins, and low concentrations of high-density lipoproteins. One proposed dietary strategy for decreasing risk factors involves replacing a portion of dietary saturated fatty acids with mono- and polyunsaturated fatty acids (PUFAs). The essential omega-6 PUFA, linoleic acid (LA), is suggested to decrease the risk for CVD by affecting these lipid risk markers. Reviewing human intervention trials will provide further evidence of the effects of LA consumption on risk factors for CVD. PubMed was used to search for peer-reviewed articles. The purpose of this review was: (1) To summarize human intervention trials that studied the effects of LA consumption on lipid risk markers for CVD in healthy individuals, (2) to provide mechanistic details, and (3) to provide recommendations regarding the consumption of LA to decrease the lipid risk markers for CVD. The results from this review provided evidence that LA consumption decreases CVD lipid risk markers in healthy individuals.

Topics: Adolescent; Adult; Biomarkers; Cardiovascular Diseases; Clinical Trials as Topic; Diet; Diet Surveys; Dietary Fats, Unsaturated; Eating; Female; Healthy Volunteers; Heart Disease Risk Factors; Humans; Linoleic Acid; Lipids; Male; Middle Aged; Young Adult

Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.. We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).. In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.. In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

Topics: Aged; Arachidonic Acid; Biomarkers; Cardiovascular Diseases; Diet, Healthy; Dietary Fats; Female; Humans; Linoleic Acid; Male; Middle Aged; Nutritive Value; Observational Studies as Topic; Primary Prevention; Protective Factors; Recommended Dietary Allowances; Risk Assessment; Risk Factors; Risk Reduction Behavior

The well-known health effects of the long-chain, marine omega-3 (n-3) fatty acids (FAs) has led to a growing interest in the prognostic value that blood levels of these FAs might have vis-à-vis cardiovascular and neurocognitive diseases. The measurement and expression of n-3 FA levels is not straight-forward, however, and a wide variety of means of expression of n-3 FA status have been used in research and clinical medicine. This has led to considerable confusion as to what "optimal" n-3 FA status is. The n-6:n-3 ratio has enjoyed relatively widespread use, but this apparently simple metric has both theoretical and practical difficulties that have contributed to misunderstandings in this field. Just as the once-popular polyunsaturated:saturated FA ratio has largely disappeared from the nutritional and medical literature, it may be time to replace the n-6:n-3 ratio with a newer metric that focuses on the primary deficiency in Western diets - the lack of eicosapentaenoic and docosahexaenoic acids (EPA and DHA). The Omega-3 Index (red blood cell EPA+DHA) has much to recommend it in this regard.

Topics: Arachidonic Acid; Biomarkers; Cardiovascular Diseases; Dietary Fats; Docosahexaenoic Acids; Eicosapentaenoic Acid; Erythrocytes; Humans; Linoleic Acid; Neurodegenerative Diseases; Reference Values

Dietary fat quality, especially the intake of specific types of fatty acids, impacts the risk of many chronic diseases, including cardiovascular diseases, certain cancers and type 2 diabetes (T2DM). A recent pooled analysis involving 20 studies from around the world revealed that higher linoleic acid (18:2n-6 LA) biomarker is associated with dose-dependent decreases in the incidence of T2DM. This latest study corroborates earlier cross-sectional studies and intervention trials showing that biomarkers of LA intake are associated with reduced risk of T2DM and better glycemic control and/or insulin sensitivity. This review highlights key clinical trials that have evaluated the role of LA in glycemia and the related condition, insulin sensitivity.

Topics: Blood Glucose; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dietary Fats; Humans; Insulin Resistance; Linoleic Acid; Neoplasms; Risk

Dietary fatty acids are associated with the development of many chronic diseases, such as obesity, diabetes, cardiovascular disease, metabolic syndrome, and several cancers. This review explores the literature surrounding the combined and individual roles of n-6 PUFAs linoleic acid (LA) and arachidonic acid (AA) as they relate to immune and inflammatory response, cardiovascular health, liver health, and cancer. The evidence suggests that a pro-inflammatory view of LA and AA may be over simplified. Overall, this review highlights gaps in our understanding of the biological roles of LA, AA and their complex relationship with n-3 PUFA and the need for future studies that examine the roles of individual fatty acids, rather than groups.

Topics: Animals; Arachidonic Acid; Cardiovascular Diseases; Dietary Fats, Unsaturated; Gene Knockout Techniques; Humans; Inflammation; Linoleic Acid; Linoleoyl-CoA Desaturase; Liver Diseases; Neoplasms

The aim of this review was to determine the impact of the fatty acid desaturase (FADS) genotype on plasma and tissue concentrations of the long-chain (LC) n-3 PUFA, including EPA and DHA, which are associated with the risk of several diet-related chronic diseases, including CVD. In addition to dietary intakes, which are low for many individuals, tissue EPA and DHA are also influenced by the rate of bioconversion from α-linolenic acid (αLNA). Δ-5 and Δ-6 desaturase enzymes, encoded for by FADS1 and FADS2 genes, are key desaturation enzymes involved in the bioconversion of essential fatty acids (αLNA and linoleic acid (LA)) to longer chained PUFA. In general, carriers of FADS minor alleles tend to have higher habitual plasma and tissue levels of LA and αLNA, and lower levels of arachidonic acid, EPA and also to a lesser extent DHA. In conclusion, available research findings suggest that FADS minor alleles are also associated with reduced inflammation and CVD risk, and that dietary total fat and fatty acid intake have the potential to modify relationships between FADS gene variants and circulating fatty acid levels. However to date, neither the size-effects of FADS variants on fatty acid status, nor the functional SNP in FADS1 and 2 have been identified. Such information could contribute to the refinement and targeting of EPA and DHA recommendations, whereby additional LC n-3 PUFA intakes could be recommended for those carrying FADS minor alleles.

Topics: alpha-Linolenic Acid; Arachidonic Acid; Cardiovascular Diseases; Delta-5 Fatty Acid Desaturase; Diet; Dietary Fats; Fatty Acid Desaturases; Fatty Acids; Fatty Acids, Omega-3; Genotype; Health Status; Humans; Linoleic Acid; Nutritional Status

The "modern western" diet (MWD) has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6) 18 carbon (C18), polyunsaturated fatty acid (PUFA) linoleic acid (LA; 18:2n-6), with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD). Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

Topics: Animals; Black or African American; Cardiovascular Diseases; Diet; Disease Models, Animal; Fatty Acids, Omega-6; Gene-Environment Interaction; Health Status Disparities; Humans; Linoleic Acid; Risk Factors

According to the classic "diet-heart" hypothesis, high dietary intake of saturated fats and cholesterol combined with low intake of polyunsaturated fats can increase levels of serum cholesterol and lead to the development of atherogenic plaques and ultimately cardiovascular diseases. Recently, the beneficial health effects of omega-6 polyunsaturated fatty acids, particularly linoleic acid (LA), on cardiovascular health have been called into question with some scientists suggesting that consumption of LA should be reduced in Western countries. The focus of this critical review is on the controversy surrounding the effects of dietary intake of LA on cardiovascular health. Specifically, we critically examined the effects of both unadulterated and adulterated forms of LA on cardiovascular health outcomes based on findings from epidemiological studies and randomized controlled trials. Additionally, we address common concerns surrounding dietary intake of LA regarding its relationship with arachidonic acid, the ratio of omega-6 to omega-3 fatty acids, and its relationship with inflammation. Our critical review indicates that unadulterated forms of LA are cardioprotective and should be consumed as part of a healthy diet. In contrast, abundant evidence now indicates that adulterated forms of LA, predominantly hydrogenated vegetable oils, are atherogenic and should not be considered part of a healthy diet. The ability to adulterate the natural omega-6 fatty acid, LA, has contributed to mixed findings regarding the effects of this fatty acid on cardiovascular health. Thus, it is critical that the source of LA be taken into account when drawing conclusions about the physiological effects of this fatty acid. The findings of the present review are in line with current dietary recommendations of the American Heart Association.

Topics: Cardiovascular Diseases; Dietary Fats; Humans; Linoleic Acid; Randomized Controlled Trials as Topic

This review asks the question if further research on trans fatty acids and cardiovascular health is needed. We therefore review the evidence from human studies on trans fatty acids and cardiovascular health, and provide a quantitative review of effects of trans fatty acid intake on lipoproteins. The results show that the effect of industrially produced trans fatty acids on heart health seen in observational studies is larger than predicted from changes in lipoprotein concentrations. There is debate on the effect of ruminant trans fatty acids and cardiovascular disease. Of special interest is conjugated linoleic acid (CLA), which is produced industrially for sale as supplements. Observational studies do not show higher risks of cardiovascular disease with higher intakes of ruminant trans fatty acids. However, CLA, industrial and ruminant trans fatty acids all raise plasma low-density lipoprotein and the total to high-density lipoprotein ratio. Gram for gram, all trans fatty acids have largely the same effect on blood lipoproteins. In conclusion, the detrimental effects of industrial trans fatty acids on heart health are beyond dispute. The exact size of effect will remain hard to determine. Further research is warranted on the effects of ruminant trans fatty acids and CLA on cardiovascular disease and its risk factors.

Topics: Animals; Cardiovascular Diseases; Dietary Supplements; Heart; Humans; Linoleic Acid; Linoleic Acids, Conjugated; Lipoproteins, HDL; Lipoproteins, LDL; Trans Fatty Acids

This review addresses the cardiovascular benefits of the two families of essential polyunsaturated fatty acids (FAs): omega-6 and omega-3. The former (and the shorter chain species of the latter) are found in vegetable oils and nuts, whereas the longer chain omega-3 FAs are found in fish oils. Although most clinicians understand that the omega-3 FAs are beneficial, there have been calls in the popular press to reduce the intake of the omega-6 FAs because of presumed proinflammatory and prothrombotic effects.. The American Heart Association's Nutrition Committee has published two 'Science Advisories', one in 2002 on omega-3 FAs and a new one on omega-6 FAs. Both considered a wide variety of data regarding their effects on cardiac risk.. The AHA concludes that Americans need to increase their intake of long-chain omega-3 FAs and that they should maintain (and possibly even increase) their intakes of omega-6 FAs. For the omega-3 FAs, a healthy target intake is about 500 mg per day (whether from oily fish or fish oil capsules) and for linoleic acid, approximately 15 g per day (12 g for women and 17 g for men). Achieving healthy intakes of both omega-6 and omega-3 FAs is an important component of the nutritional prevention and treatment of coronary heart disease.

Topics: Cardiovascular Diseases; Dietary Fats; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Linoleic Acid; Male

n-6 PUFA are well known for their critical role in many physiological functions and seem to reduce risks of CHD. However, some argue that excessive consumption of n-6 PUFA may lead to adverse effects on health and therefore recommend reducing dietary n-6 PUFA intake or fixing an upper limit. In this context, the present work aimed to review evidence on the link between n-6 PUFA and risks of CVD. Epidemiological studies show that n-6 PUFA dietary intake significantly lowers blood LDL-cholesterol levels. In addition, n-6 PUFA intake does not increase several CVD risk factors such as blood pressure, inflammatory markers, haemostatic parameters and obesity. Data from prospective cohort and interventional studies converge towards a specific protective role of dietary n-6 PUFA intake, in particular linoleic acid, against CVD. n-6 PUFA benefits are even increased when SFA intake is also reduced. In regards to studies examined in this narrative review, recommendation for n-6 PUFA intake above 5 %, and ideally about 10 %, of total energy appears justified.

Topics: Cardiovascular Diseases; Dietary Fats; Fatty Acids; Fatty Acids, Omega-6; Humans; Linoleic Acid; Nutrition Policy; Risk Factors

Topics: Arachidonic Acid; Atherosclerosis; Biological Evolution; Brain; Cardiovascular Diseases; Diet; Dietary Fats; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Gene Expression; Gene Expression Regulation; Genetic Variation; Humans; Inflammation; Linoleic Acid; Nutrition Policy; Nutritional Requirements; Trans Fatty Acids

Several sources of information suggest that human beings evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of approximately 1 whereas in Western diets the ratio is 15/1-16.7/1. Western diets are deficient in omega-3 fatty acids, and have excessive amounts of omega-6 fatty acids compared with the diet on which human beings evolved and their genetic patterns were established. Excessive amounts of omega-6 polyunsaturated fatty acids (PUFA) and a very high omega-6/omega-3 ratio, as is found in today's Western diets, promote the pathogenesis of many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 PUFA (a lower omega-6/omega-3 ratio), exert suppressive effects. In the secondary prevention of cardiovascular disease, a ratio of 4/1 was associated with a 70% decrease in total mortality. A ratio of 2.5/1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4/1 with the same amount of omega-3 PUFA had no effect. The lower omega-6/omega-3 ratio in women with breast cancer was associated with decreased risk. A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5/1 had a beneficial effect on patients with asthma, whereas a ratio of 10/1 had adverse consequences. These studies indicate that the optimal ratio may vary with the disease under consideration. This is consistent with the fact that chronic diseases are multigenic and multifactorial. Therefore, it is quite possible that the therapeutic dose of omega-3 fatty acids will depend on the degree of severity of disease resulting from the genetic predisposition. A lower ratio of omega-6/omega-3 fatty acids is more desirable in reducing the risk of many of the chronic diseases of high prevalence in Western societies, as well as in the developing countries.

Topics: alpha-Linolenic Acid; Biological Evolution; Blood Platelets; Cardiovascular Diseases; Cell Proliferation; Chronic Disease; Colorectal Neoplasms; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Humans; Linoleic Acid; Models, Biological; Platelet Aggregation; Risk

n-6 Fatty acids, like n-3 fatty acids, play essential roles in many biological functions. Because n-6 fatty acids are the precursors of proinflammatory eicosanoids, higher intakes have been suggested to be detrimental, and the ratio of n-6 to n-3 fatty acids has been suggested by some to be particularly important. However, this hypothesis is based on minimal evidence, and in humans higher intakes of n-6 fatty acids have not been associated with elevated levels of inflammatory markers. n-6 Fatty acids have long been known to reduce serum total and low-density lipoprotein cholesterol, and increases in polyunsaturated fat intake, mostly as n-6 fatty acids, were a cornerstone of dietary advice during the 1960s and 1970s. In the United States, for example, intake of n-6 fatty acids doubled and coronary heart disease (CHD) mortality fell by 50% over a period of several decades. In a series of relatively small, older randomized trials, in which intakes of polyunsaturated fat were increased (even up to 20% of calories), rates of CHD were generally reduced. In a more recent detailed examination of fatty acid intake within the Nurses' Health Study, greater intake of linoleic acid, up to about 8% of energy, has been strongly related to lower incidence of myocardial infarction or CHD death. Because n-3 fatty acids were also related inversely to risk of CHD, the ratio was unrelated to risk. n-6 Fatty acids reduce insulin resistance, probably by acting as a ligand for peroxisome proliferator-activated receptors-gamma, and intakes have been inversely related to risk of type 2 diabetes. Adequate intakes of both n-6 and n-3 fatty acids are essential for good health and low rates of cardiovascular disease and type 2 diabetes, but the ratio of these fatty acids is not useful. Reductions of linoleic acid to "improve" this ratio would likely increase rates of cardiovascular disease and diabetes.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fatty Acids, Omega-6; Humans; Inflammation; Insulin Resistance; Linoleic Acid; Lipids; NF-kappa B; Receptors, Tumor Necrosis Factor

Epidemiologic studies have shown a beneficial association between polyunsaturated fatty acid (PUFA), specifically linoleic acid (C18:2, n-6), intake and cardiovascular disease morbidity and mortality. Clinical studies have shown that n-6 PUFAs have the most potent cholesterol-lowering effects of the individual fatty acid classes, and emerging evidence suggests that PUFAs have favorable effects on postprandial lipemia. However, some studies suggest that high intakes of linoleic acid may have adverse effects on proinflammatory cytokines and adhesion molecules. Research is needed to establish the optimal level of dietary PUFAs that maximally affects the greatest number of health risk factors.

Topics: Cardiovascular Diseases; Cell Adhesion Molecules; Cholesterol; Clinical Trials as Topic; Cytokines; Dietary Fats, Unsaturated; Epidemiologic Studies; Fatty Acids, Unsaturated; Humans; Linoleic Acid; Oxidative Stress; Risk Factors

Analysis of the fatty acid composition of serum lipid fractions is an old but still useful method for several purposes. The proportions of essential polyunsaturated and trans fatty acids are biomarkers of dietary intake that can be used to improve estimates of fatty acid intake in dietary trials and population studies. Furthermore, the metabolism of essential n-6 and n-3 fatty acids is reflected in the serum fatty acid composition. Changes in the activity of the delta-6 and delta-5 desaturases, which affect the proportions of dihomogamma-linolenic acid and arachidonic acid in serum lipids, are associated with insulin resistance and may explain differences in coronary heart disease risk.

Topics: Biomarkers; Cardiovascular Diseases; Dietary Fats; Fatty Acids; Humans; Linoleic Acid; Lipids

Conjugated linoleic acid (CLA) refers to a group of positional and geometric isomers of the omega-6 essential fatty acid linoleic acid (cis-9, cis-12, octadecadienoic acid). In humans evidence is currently ambiguous as to whether CLA supplementation has a significant effect on body composition. Despite favorable changes in lipid levels in animal models, a beneficial effect in humans has not yet been established. While some of the changes reported are consistent with an improved lipid profile, declines in HDL and increases in lipoprotein (a) have also been observed in some subjects. Available evidence suggests CLA supplementation has no impact on immune system performance in healthy subjects.

Topics: Animals; Body Composition; Cardiovascular Diseases; Dietary Supplements; Dose-Response Relationship, Drug; Humans; Insulin Resistance; Linoleic Acid; Neoplasms

N-6 fatty acids are essential for normal growth, development and health, and so extreme care is necessary before deciding that they are harmful. Theoretical and epidemiological evidence suggests the involvement of n-6 polyunsaturated fatty acids (PUFAs) in disease progression or prevention; however, n-6 function cannot be considered in isolation but needs to be seen as part of the complex of nutrient interactions with n-3 fatty acids (which compete for the same enzymatic pathways) and antioxidants. Insulin sensitivity might be the common factor relating disease to fatty acid metabolism both within and between the fatty acid pathways. High linoleate to arachidonate concentrations have been observed in insulin resistance, diabetic complications and some tumours, but these are multifactorial processes that include many lifestyle determinants and it is therefore wrong to condemn only n-6 fatty acids in their etiology. The results based on the criteria for assessing diet and disease are still insufficient to declare n-6 fatty acids a serious health risk; at most, the verdict should be "not proven". The question may never be conclusively answered not only because prospective dietary intervention trials (unlike those with n-3 fish oil capsules) are fraught with dosage and compliance problems, but also because of high background linoleate consumption. Tissue fatty acid composition may be a suitable biomarker for PUFA intake but there are many theoretical and methodological problems concerning other suitable markers because of the multiplicity of their biological effects. Before making evidence-based dietary recommendations, future research should consider: 1) how n-3 and n-6 dietary PUFAs affect the physiological balance (dose-response) of their derivatives such as eicosanoids and the newly-discovered fatty acid amides; 2) the metabolic interactions between n-6 and n-3 fatty acid pathways (including gene-nutrient effects); 3) the need for antioxidant cover (quantity and quality); 4) prospective intervention trials.

Topics: Animals; Arteriosclerosis; Cardiovascular Diseases; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Humans; Insulin Resistance; Linoleic Acid; Neoplasms

Milk is often seen as a potential promotor of atherosclerosis and coronary heart disease because it is a source of cholesterol and saturated fatty acids. But there are several studies indicating that milk and milk products may not affect adversely blood lipids as would be predicted from its fat content and fat composition. There are even factors in milk and milk products which may actively protect from this condition by improving several risk factors. Calcium, bioactive peptides and as yet unidentified components in whole milk may protect from hypertension, and folic acid, vitamin B6 (pyridoxine) and B12 (cyanocobalamin) or other unidentified components of skim milk may contribute to low homocysteine levels. Conjugated linoleic acid may have hypolipidaemic and antioxidative and thus antiatherosclerotic properties. Epidemiological studies suggest that milk and milk products fit well into a healthy eating pattern emphasizing cereals and vegetables.

Topics: Animals; Anticholesteremic Agents; Antioxidants; Arteriosclerosis; Calcium; Cardiovascular Diseases; Coronary Disease; Diet; Humans; Hypertension; Linoleic Acid; Milk; Milk Proteins; Risk Factors; Vitamins

Higher circulating linoleic acid (LA) and muscle-derived tetralinoleoyl-cardiolipin (LA. 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 LA. LA-rich oil fortification increases while OA-oil has no effect on LA

Topics: Adult; Cardiolipins; Cardiovascular Diseases; Fatty Acids; Humans; Leukocytes, Mononuclear; Linoleic Acid; Oleic Acid

Plant oil for cooking typically provides 40% to 50% of dietary fat, 65% of linoleic acid, 44% of α-linolenic acid and 41% of oleic acid in the Chinese diet. However, the comparative effects of fatty acids derived from plant oil on cardiovascular risk factors in Chinese are still inconclusive. Hence, the aim of this study is to investigate whether cardiovascular risk factors are altered depending on various types of plant oils such as peanut oil rich in oleic acid, corn oil rich in linoleic acid, and blend oil fortified by α-linolenic acid.. A randomized, double-blinded, parallel-designed trial.. The First and the Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.. A total of 251 volunteers with fasting blood total cholesterol between 5.13 and 8.00 mmol L. Volunteers received peanut oil, corn oil or blend oil to use for cooking for one year.. The erythrocyte membrane fatty acid composition, fasting plasma lipids, glucose and insulin concentrations and high sensitivity C-reactive protein (hsCRP) levels were measured before, during and after the intervention. The level of α-linolenic acid in erythrocyte membranes was significantly increased in the blend oil group after the intervention (P < 0.001). The level of other fatty acids did not show any statistically significant differences between the three groups. No significant differences were observed in the concentrations of fasting plasma lipids, hsCRP, glucose, and insulin among the three groups using different types of plant oils.. The results suggest that although ingesting cooking oil with different fatty acid composition for one year could change erythrocyte membrane fatty acid compositions, it did not significantly modify cardiovascular risk factors in moderately hypercholesteremic people.

Topics: Adult; Aged; alpha-Linolenic Acid; Asian People; Cardiovascular Diseases; China; Cholesterol; Corn Oil; Diet, Fat-Restricted; Dietary Fats; Double-Blind Method; Fasting; Fatty Acids; Female; Heart Disease Risk Factors; Humans; Hypercholesterolemia; Linoleic Acid; Male; Middle Aged; Oleic Acid; Peanut Oil; Plant Oils

Oleic acid consumption is considered cardio-protective according to studies conducted examining effects of the Mediterranean diet. However, animal models have shown that oleic acid consumption increases LDL particle cholesteryl oleate content which is associated with increased LDL-proteoglycan binding and atherosclerosis. The objective was to examine effects of varying oleic, linoleic and docosahexaenoic acid consumption on human LDL-proteoglycan binding in a non-random subset of the Canola Oil Multi-center Intervention Trial (COMIT) participants. COMIT employed a randomized, double-blind, five-period, cross-over trial design. Three of the treatment oil diets: 1) a blend of corn/safflower oil (25:75); 2) high oleic canola oil; and 3) DHA-enriched high oleic canola oil were selected for analysis of LDL-proteoglycan binding in 50 participants exhibiting good compliance. LDL particles were isolated from frozen plasma by gel filtration chromatography and LDL cholesteryl esters quantified by mass-spectrometry. LDL-proteoglycan binding was assessed using surface plasmon resonance. LDL particle cholesterol ester fatty acid composition was sensitive to the treatment fatty acid compositions, with the main fatty acids in the treatments increasing in the LDL cholesterol esters. The corn/safflower oil and high-oleic canola oil diets lowered LDL-proteoglycan binding relative to their baseline values (p = 0.0005 and p = 0.0012, respectively). At endpoint, high-oleic canola oil feeding resulted in lower LDL-proteoglycan binding than corn/safflower oil (p = 0.0243) and DHA-enriched high oleic canola oil (p = 0.0249), although high-oleic canola oil had the lowest binding at baseline (p = 0.0344). Our findings suggest that high-oleic canola oil consumption in humans increases cholesteryl oleate percentage in LDL, but in a manner not associated with a rise in LDL-proteoglycan binding.

Topics: Adult; Canada; Cardiovascular Diseases; Cholesterol Esters; Cholesterol, LDL; Corn Oil; Cross-Over Studies; Diet, Mediterranean; Dietary Fats; Docosahexaenoic Acids; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Humans; Linoleic Acid; Male; Middle Aged; Oleic Acid; Proteoglycans; Rapeseed Oil; Risk Factors; Risk Reduction Behavior; Safflower Oil; Time Factors; United States

The current study aimed to evaluate the effect of fortified milk combined with a lifestyle and counselling programme on several CVD risk factors after a 3-month dietary intervention.. Hypercholesterolaemic adults were randomized to a group supplemented with low-fat milk that was enriched with phytosterols, α-linolenic and linoleic fatty acids, vitamins and antioxidants (enriched milk group, EMG: n 40), a placebo milk group (PMG: n 36) or a control group (CG: n 25). The EMG and PMG consumed respectively 500 ml of enriched milk or placebo milk daily and attended biweekly counselling sessions over a 3-month period.. Harokopio University, Athens, Greece.. A sample of 101 hypercholesterolemic adults aged 40-60 years.. Regarding lifestyle changes, total and saturated fat intakes decreased significantly in both intervention groups compared with the CG (P < 0·005). Furthermore, total steps were increased (P = 0·029) and BMI was decreased (P = 0·017) significantly in both intervention groups compared with the CG. Regarding biochemical indices, EPA content in erythrocyte membranes increased (P < 0·001) while serum C-reactive protein decreased (P = 0·003) significantly in both intervention groups compared with the CG. Finally, significant increases in plasma folic acid and vitamin B12 levels and a significant decrease in homocysteine levels were observed in the EMG compared with the PMG and CG (all P < 0·001). A favourable change in LDL cholesterol:HDL cholesterol was also observed in the EMG and tended to be significant compared with the PMG and CG (P = 0·066).. The present study showed that consumption of fortified milk accompanied with lifestyle counselling induces extra benefits in terms of LDL cholesterol:HDL cholesterol and serum homocysteine levels.

Topics: Adult; alpha-Linolenic Acid; Animals; Antioxidants; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Female; Food, Fortified; Humans; Life Style; Linoleic Acid; Male; Middle Aged; Milk; Motor Activity; Nutrition Assessment; Phytosterols; Risk Factors; Triglycerides

Enhanced n-3 fatty acid intake benefits cardiovascular disease (CVD) risk reduction. Increasing consumption at a population level may be better addressed by diet than through supplementation. However, limited data are available on the effect of the dose response to fish intake on plasma levels of n-3 fatty acids. To compare the effects of different doses of farmed Atlantic salmon on plasma phospholipid fatty acid proportions and CVD risk biomarkers (eg, glucose, insulin, homeostasis model of assessment-insulin resistance, high-sensitivity C-reactive protein, and interleukin-6) in healthy subjects we performed a randomized three-period crossover-designed trial (4-week treatment, 4- to 8-week washout) to compare the effects of twice per week consumption of farmed Atlantic salmon at doses of 90, 180, and 270 g in 19 apparently healthy men and women (mean age 40 to 65 years) and a body mass index between 25 and 34.9. All study visits were conducted at the US Department of Agriculture Agricultural Research Service Grand Forks Human Nutrition Research Center. Eicosapentaenoic acid and total n-3 concentrations were increased (P<0.05) by all treatments in a dose-response manner, with total n-3 of 8.03% ± 0.26% and 9.21% ± 0.26% for 180- and 270-g doses, respectively. Linoleic acid did not change in response to treatment, whereas arachidonic acid (P<0.05) and total n-6 fatty acids decreased dose dependently (<0.0001). The addition of farmed Atlantic salmon to the diet twice per week for 4 weeks at portions of 180 g and 270 g modifies phospholipid fatty acid proportions of n-3 and n-6 in a level associated with decreased risk for CVD.

Topics: Adult; Aged; Animals; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cross-Over Studies; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Insulin; Interleukin-6; Linoleic Acid; Male; Middle Aged; Salmo salar; Seafood; Triglycerides

Polyunsaturated fatty acids (PUFA) have beneficial effects on cardiovascular risk, although the mechanisms are incompletely understood. In a previous article, we showed significant reductions in low-density lipoprotein cholesterol and several markers of inflammation with increasing intake of alpha-linolenic acid (ALA) from walnuts and flax.. To examine effects of ALA on cardiovascular responses to acute stress, flow-mediated dilation (FMD) of the brachial artery, and blood concentrations of endothelin-1 and arginine-vasopressin (AVP).. Using a randomized, crossover study design, cardiovascular responses to acute stress were assessed in 20 hypercholesterolemic subjects, a subset of whom also underwent FMD testing (n  =  12). Participants were fed an average American diet (AAD) and 2 experimental diets that varied in the amount of ALA and linoleic acid (LA) that they contained. The AAD provided 8.7% energy from PUFA (7.7% LA, 0.8% ALA). On the LA diet, saturated fat was reduced, and PUFA from walnuts and walnut oil provided 16.4% of energy (12.6% LA, 3.6% ALA). On the ALA diet, walnuts, walnut oil, and flax oil provided 17% energy from PUFA (10.5% LA, 6.5% ALA).. The ALA and LA diets significantly reduced diastolic blood pressure (-2 to -3 mm Hg) and total peripheral resistance (-4%), and this effect was evident at rest and during stress (main effect of diet, p < 0.02). FMD increased (+34%) on the diet containing additional ALA. AVP also increased by 20%, and endothelin-1 was unchanged.. These results suggest novel mechanisms for the cardioprotective effects of walnuts and flax, and further work is needed to identify the bioactives responsible for these effects.

Topics: alpha-Linolenic Acid; Biomarkers; Blood Pressure; Cardiovascular Diseases; Cholesterol, LDL; Cross-Over Studies; Diet; Endothelin-1; Flax; Humans; Hypercholesterolemia; Juglans; Linoleic Acid; Middle Aged; Nuts; Plant Oils; Risk Factors; Stress, Psychological; Vascular Resistance

Both (n-3) long-chain PUFA (LCPUFA) and linoleic acid [LA, 18:2(n-6)] improve cardiovascular disease (CVD) risk factors, but a high-LA intake may weaken the effect of (n-3) LCPUFA. In a controlled, double-blind, 2 x 2-factorial 8-wk intervention, we investigated whether fish oil combined with a high- or low-LA intake affects overall CVD risk profile. Healthy men (n = 64) were randomized to 5 mL/d fish oil capsules (FO) [mean intake 3.1 g/d (n-3) LCPUFA] or olive oil capsules (control) and to oils and spreads with either a high (S/B) or a low (R/K) LA content, resulting in a 7.3 g/d higher LA intake in the S/B groups than in the R/K groups. Diet, (n-3) LCPUFA in peripheral blood mononuclear cells, blood pressure (BP), heart rate (HR), and plasma CVD risk markers were measured before and after the intervention. FO lowered fasting plasma triacylglycerol (TAG) (P < 0.001) by 51% and 19% in the FO+R/K-group and FO+S/B-group, respectively, which was also reflected in postprandial TAG measured after the intervention (P < 0.01). Although a fat x FO interaction was found for monocyte chemoattractant protein-1, neither the FO nor fat intervention affected fasting plasma cholesterol, glucose, insulin, fibrinogen, C-reactive protein, interleukin-6, vascular cell adhesion molecule-1, P-selectin, oxidized LDL, cluster of differentiation antigen 40 ligand (CD40L), adiponectin, or fasting or postprandial BP or HR after adjustment for body weight changes. In conclusion, neither fish oil supplementation nor the LA intake had immediate pronounced effects on the overall CVD risk profile in healthy men, but fish oil lowered plasma TAG in healthy subjects with initially low concentrations.

Topics: Adult; Biomarkers; Cardiovascular Diseases; Diet; Dietary Supplements; Double-Blind Method; Fish Oils; Humans; Hypertriglyceridemia; Linoleic Acid; Male; Risk Factors; Triglycerides

Previous studies have demonstrated benefits of high-dose long-chain omega-3 polyunsaturated fatty acid (LC omega-3 PUFA) supplements on metabolic risk. Effects of increased dietary omega-3 PUFA, via oily fish and/or plant-derived omega-3 PUFAs, are less clear and may be modulated by the omega-6:omega-3 PUFA of the habitual diet. This study examined the effect on cardiovascular disease risk markers of reducing dietary omega-6:omega-3 PUFA by changes in linoleic acid:alpha-linolenic acid (LA:LNA) and/or increasing LC omega-3 PUFA. It tested whether decreases in LA:LNA modulate effects of LC omega-3 PUFA.. One hundred forty-two subjects, recruited to a 24-wk randomized study, were assigned to a control group or one of four interventions. Intervention groups received two portions of oily fish (4.5 g eicosapentaenoic acid + docosahexanoic acid) or white fish (0.7 g eicosapentaenoic acid + docosahexanoic acid) per week, and replaced habitual household fats with ones high in sunflower (high LA:LNA) or rapeseed (low LA:LNA) oil.. Modest dietary manipulations of omega-6 and omega-3 PUFAs resulted in significant group x time interactions for serum triacylglycerols (TAGs; P = 0.05); at 24 wk the control and two oily fish groups showed lower TAG than did the white fish/sunflower group (P = 0.05). Reductions in TAG, associated with increased oily fish intakes, were maximized when combined with lower dietary LA:LNA. There were no significant changes in several other cardiovascular disease risk markers.. Two portions of oily fish per week led to significant reductions in TAG relative to consumption of two portions of white fish per week. Changes in TAG were maximized when combined with lower LA:LNA.

Topics: alpha-Linolenic Acid; Biomarkers; Cardiovascular Diseases; Dietary Fats, Unsaturated; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Fish Oils; Humans; Linoleic Acid; Male; Middle Aged; Obesity; Plant Oils; Rapeseed Oil; Risk Factors; Sunflower Oil; Triglycerides

Abdominal obesity is strongly related to metabolic disorders. Recent research suggests that dietary conjugated linoleic acid (CLA) reduces body fat and may improve metabolic variables in animals. The metabolic effects of CLA in abdominally obese humans have not yet been tested.. To investigate the short-term effect of CLA on abdominal fat and cardiovascular risk factors in middle-aged men with metabolic disorders.. Twenty-five abdominally obese men (waist-to-hip ratio (WHR), 1.05+/-0.05; body mass index (BMI), 32+/-2.7 kg/m(2) (mean+/-s.d.)) who were between 39 and 64-y-old participated in a double-blind randomised controlled trial for 4 weeks. Fourteen men received 4.2 g CLA/day and 10 men received a placebo. The main endpoints were differences between the two groups in sagittal abdominal diameter (SAD), serum cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, free fatty acids, glucose and insulin.. At baseline, there were no significant differences between groups in anthropometric or metabolic variables. After 4 weeks there was a significant decrease in SAD (cm) in the CLA group compared to placebo (P=0.04, 95% CI; -1.12, -0.02). Other measurements of anthropometry or metabolism showed no significant differences between the groups.. These results indicate that CLA supplementation for 4 weeks in obese men with the metabolic syndrome may decrease abdominal fat, without concomitant effects on overall obesity or other cardiovascular risk factors. Because of the limited sample size, the effects of CLA in abdominal obesity need to be further investigated in larger trials with longer duration.

Topics: Adipose Tissue; Adult; Blood Glucose; Body Constitution; Cardiovascular Diseases; Humans; Insulin; Linoleic Acid; Lipids; Male; Middle Aged; Obesity; Risk Factors

To determine the effects of feeding regimens of varying fat composition on dietary intake and serum lipid and lipoprotein concentrations in older infants.. One hundred four healthy infants aged 4 to 6 months were enrolled from private pediatric practices or public health clinics and were randomly assigned to one of four feeding groups until 12 months of age.. Infants received whole cow milk or a standard infant formula (48% to 49% of energy as fat from butterfat or a soy-coconut oil blend, respectively) or one of two nearly identical investigational lower fat follow-up formulas (36% kcal from a fat blend of palm olein, corn, and safflower oils) as their primary food source in addition to table foods.. Nutrient intakes during the study period were characterized qualitatively and quantitatively. Serum lipids, lipoprotein concentrations, and anthropometrics were determined at baseline and at 12 months of age (study completion).. Total energy intake was equivalent among feeding groups. Infants fed cow milk had higher mean daily intakes of total fat, saturated fat, monounsaturated fat, and cholesterol. Linoleic acid intake by infants fed cow milk, including that from table foods, was insufficient to meet current recommendations. Mean serum total cholesterol was significantly higher in the infants fed cow milk at age 12 months, whereas mean low density lipoprotein and apolipoprotein B were lower in the infants fed the follow-up formulas. Infants consuming the infant formula or whole cow milk demonstrated greater increases in mean serum total cholesterol, low density lipoprotein, and apolipoprotein B by 12 months of age compared with infants ingesting follow-up formula. Ponderal, linear, and head circumference growth was equivalent among feeding groups.. (1) Older infants fed lower fat formula have adequate total energy intake and normal growth. (2) The fat composition of the diets fed to the infants influenced serum lipid and lipoprotein profiles. (3) The fat composition of cow milk is inferior compared with commercial formulas. (4) The optimal fat blend for older infants including the consequences of the standard practice of adding high percentage of coconut oil to infant formulas should be defined further.

Topics: Animals; Cardiovascular Diseases; Dietary Fats; Energy Intake; Humans; Infant; Infant Food; Linoleic Acid; Linoleic Acids; Lipids; Milk; Risk Factors

Effects of a daily fish-oil supplement on serum lipids, apolipoproteins, and some platelet functions and hemorheologic variables were examined in 27 hyperlipidemic subjects in a randomized, controlled, double-blind, crossover fashion with an identically encapsulated vegetable oil serving as the control treatment. Despite the habitual high linoleic acid intake of the study population, significant incorporation of n-3 (omega-3) fatty acids into the serum, platelet, and erythrocyte lipids was observed after the fish-oil supplement. Ingestion of fish oil resulted in a 40% decrease in the triglyceride concentration, a 12% increase in HDL cholesterol, and a significant decrease in plasma viscosity, whereas the vegetable-oil placebo had no significant effect. We conclude that a moderate intake of fish oil (15 g/d) is a feasible treatment for hypertriglyceridemia even in patients with a background of high linoleic acid intake and that it may have a beneficial effect on several cardiovascular risk factors.

Topics: Apolipoproteins; Blood Platelets; Blood Viscosity; Cardiovascular Diseases; Cholesterol; Double-Blind Method; Erythrocyte Deformability; Fatty Acids; Fish Oils; Humans; Hyperlipidemias; Israel; Linoleic Acid; Linoleic Acids; Lipids; Platelet Aggregation; Risk Factors; Triglycerides

Despite early interest in the health effects of polyunsaturated fatty acids (PUFA), there is still substantial controversy and uncertainty on the evidence linking PUFA to cardiovascular diseases (CVDs). We investigated the effect of plasma concentration of omega-3 PUFA (i.e. docosahexaenoic acid (DHA) and total omega-3 PUFA) and omega-6 PUFA (i.e. linoleic acid and total omega-6 PUFA) on the risk of CVDs using Mendelian randomization.. We conducted the largest genome-wide association study (GWAS) of circulating PUFA to date including a sample of 114,999 individuals and incorporated these data in a two-sample Mendelian randomization framework to investigate the involvement of circulating PUFA on a wide range of CVDs in up to 1,153,768 individuals of European ancestry (i.e. coronary artery disease, ischemic stroke, haemorrhagic stroke, heart failure, atrial fibrillation, peripheral arterial disease, aortic aneurysm, venous thromboembolism and aortic valve stenosis).. GWAS identified between 46 and 64 SNPs for the four PUFA traits, explaining 4.8-7.9% of circulating PUFA variance and with mean F statistics >100. Higher genetically predicted DHA (and total omega-3 fatty acids) concentration was related to higher risk of some cardiovascular endpoints; however, these findings did not pass our criteria for multiple testing correction and were attenuated when accounting for LDL-cholesterol through multivariable Mendelian randomization or excluding SNPs in the vicinity of the FADS locus. Estimates for the relation between higher genetically predicted linoleic acid (and total omega-6) concentration were inconsistent across different cardiovascular endpoints and Mendelian randomization methods. There was weak evidence of higher genetically predicted linoleic acid being related to lower risk of ischemic stroke and peripheral artery disease when accounting by LDL-cholesterol.. We have conducted the largest GWAS of circulating PUFA to date and the most comprehensive Mendelian randomization analyses. Overall, our Mendelian randomization findings do not support a protective role of circulating PUFA concentration on the risk of CVDs. However, horizontal pleiotropy via lipoprotein-related traits could be a key source of bias in our analyses.

Topics: Biological Specimen Banks; Cardiovascular Diseases; Cholesterol, LDL; Fatty Acids; Fatty Acids, Unsaturated; Genome-Wide Association Study; Humans; Ischemic Stroke; Linoleic Acid; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Factors; United Kingdom

Previous studies have shown distinct associations between specific dietary fats and mortality. However, evidence on specific dietary fats and mortality among patients with cardiometabolic disease (CMD) remains unclear. The aim of this study was to estimate the association between consumption of specific fatty acids and survival of patients with CMD and examine whether cardiometabolic biomarkers can mediate the above effects. The study included 8537 participants with CMD, from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999-2014. Cox proportional hazards regression, restricted cubic spline regression, and isocaloric substitution models were used to estimate the associations of dietary fats with all-cause mortality and cardiovascular disease (CVD) mortality among participants with CMD. Mediation analysis was performed to assess the potential mediating roles of cardiometabolic biomarkers. During a median follow-up of 10.3 years (0-27.1 years), 3506 all-cause deaths and 882 CVD deaths occurred. The hazard ratios (HRs) of all-cause mortality among patients with CMD were 0.85 (95% confidence interval (CI), 95% CI, 0.73-0.99;

Topics: Biomarkers; Cardiovascular Diseases; Dietary Fats; Eicosapentaenoic Acid; Fatty Acids, Omega-6; Humans; Linoleic Acid; Nutrition Surveys

Whether circulating fatty acids (FAs) play a causal role in the development of cardiovascular disease (CVD) remains unclear. We conducted a Mendelian randomisation study to explore the associations between plasma phospholipid FA levels and 15 CVDs. Summary-level data from the CARDIoGRAMplusC4D, MEGASTROKE, and Atrial Fibrillation consortia and UK Biobank were used. Sixteen single-nucleotide polymorphisms (SNPs) associated with ten plasma FAs were used as instrumental variables. SNPs in or close to the

Topics: Alleles; alpha-Linolenic Acid; Arachidonic Acid; Cardiovascular Diseases; Data Analysis; Delta-5 Fatty Acid Desaturase; Fatty Acid Desaturases; Fatty Acids; Genetic Predisposition to Disease; Humans; Linoleic Acid; Mendelian Randomization Analysis; Odds Ratio; Oleic Acid; Phospholipids; Polymorphism, Single Nucleotide; Protective Factors; Risk Factors; Stearic Acids

The effect of different individual TFA isomers on cardiovascular disease (CVD) has been a limited study, especially for stroke. We aimed to investigate the relationships between four major plasma TFA isomer (elaidic, vaccenic, palmitelaidic and linolelaidic acid) concentrations and the risk of CVD, stroke and non-stroke CVD. A cross-sectional study was conducted, utilising a nationally representative sample of US adults in the National Health and Nutrition Examination Survey. Among the 3504 participants, 304 participants self-reported CVD history. The highest quintile of elaidic acid intake was associated with a 233% higher CVD risk (p = .010). Adjusted for age, gender and race, palmitelaidic acid was associated with a decreased CVD risk, but the effect size was diminished in a subsequent analysis model. For stroke risk, we failed to identify any associations. In addition to elaidic acid, the health effect of palmitelaidic acid should be paid more attention in the future studies.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Diet; Fatty Acids, Monounsaturated; Female; Humans; Isomerism; Linoleic Acid; Male; Middle Aged; Nutrition Surveys; Oleic Acid; Oleic Acids; Risk Factors; Self Report; Trans Fatty Acids; United States; Young Adult

The cardioprotective properties of linoleic acid (LA), a major n-6 (ω-6) polyunsaturated fatty acid (PUFA), have been recognized, but less is known about its associations with other causes of death. Relatively little is also known about how the minor n-6 PUFAs-γ-linolenic acid (GLA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA)-relate to mortality risk.. We investigated the associations of serum n-6 PUFAs, an objective biomarker of exposure, with risk of death in middle-aged and older men and whether disease history modifies the associations.. We included 2480 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 y at baseline in 1984-1989. The stratified analyses by baseline disease status included 1019 men with a history of cardiovascular disease (CVD), cancer, or diabetes and 1461 men without a history of disease.. During the mean follow-up of 22.4 y, 1143 deaths due to disease occurred. Of these, 575 were CVD deaths, 317 were cancer deaths, and 251 were other-cause deaths. A higher serum LA concentration was associated with a lower risk of death from any cause (multivariable-adjusted HR for the highest compared with the lowest quintile: 0.57; 95% CI: 0.46, 0.71; P-trend < 0.001) and with deaths due to CVD (extreme-quintile HR: 0.54; 95% CI: 0.40, 0.74; P-trend < 0.001) and non-CVD or noncancer causes (HR: 0.48; 95% CI: 0.30, 0.76; P-trend = 0.001). Serum AA had similar, although weaker, inverse associations. Serum GLA and DGLA were not associated with risk of death, and none of the fatty acids were associated with cancer mortality. The results were generally similar among those with or without a history of major chronic disease (P-interaction > 0.13).. Our findings showed an inverse association of a higher biomarker of LA intake with total and CVD mortality and little concern for risk, thus supporting the current dietary recommendations to increase LA intake for CVD prevention. The finding of an inverse association of serum AA with the risk of death needs replication in other populations.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Arachidonic Acid; Biomarkers; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus; Diet; Fatty Acids, Omega-6; Follow-Up Studies; gamma-Linolenic Acid; Humans; Incidence; Linoleic Acid; Male; Middle Aged; Mortality; Neoplasms; Prospective Studies; Risk Factors; Socioeconomic Factors

Polyunsaturated fatty acids have been associated with beneficial influences on cardiovascular health. However, the underlying mechanisms are not clear, and data on the relations of polyunsaturated fatty acids to subclinical disease measures such as vascular stiffness and cardiac function are sparse and inconclusive. In a large community-based cohort, we examined the relations of omega-3 and other fatty acids to a comprehensive panel of vascular function measures (assessing microvascular function and large artery stiffness), cardiac structure and left ventricular function. Red blood cell (RBC) membrane fatty acid composition, a measure of long-term fatty acid intake, was assessed in participants of the Framingham Offspring Study and Omni cohorts and related to tonometry-derived measures of vascular stiffness and to a panel of echocardiographic traits using partial correlations. Up to n=3055 individuals (56% women, mean age 66 years) were available for analyses. In age- and sex-adjusted models, higher RBC omega-3 content was moderately associated (p≤0.002) with several measures of vascular stiffness and function in a protective direction. However, after multivariable adjustment, only an association of higher RBC omega-3 content with lower carotid-femoral pulse wave velocity (a measure of aortic stiffness) remained significant (r = -0.06, p=0.002). In secondary analyses, higher linoleic acid, the major nutritional omega-6 fatty acid, was associated with smaller left atrial size, even after multivariable adjustment (r = -0.064, p<0.001). In conclusion, in our cross-sectional community-based study, we found several associations consistent with the notion of protective effects of omega-3 and linoleic acid. The clinical significance of these modest associations remains to be elucidated.

Topics: Aged; Cardiovascular Diseases; Cross-Sectional Studies; Echocardiography, Doppler; Erythrocyte Membrane; Fatty Acids; Female; Humans; Linoleic Acid; Male; Manometry; Massachusetts; Microvessels; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Protective Factors; Pulse Wave Analysis; Risk Factors; Vascular Stiffness; Ventricular Function, Left

The unclear link between intake of polyunsaturated fatty acids (PUFAs) and risk of cardiovascular disease (CVD) could depend on genetic differences between individuals. Minor alleles of single-nucleotide polymorphisms (SNPs) in the ∆5 fatty acid desaturase (FADS) 1 gene were associated with lower blood concentrations of long-chain ω-3 (n-3) and ω-6 (n-6) PUFAs, indicating an associated loss of function effect. We examined whether the SNP rs174546 in FADS1 modifies the association between PUFA intakes and CVD risk. We included 24,032 participants (62% women, aged 44-74 y) from the Malmö Diet and Cancer cohort without prevalent CVD and diabetes. During a mean follow-up of 14 y, 2648 CVD cases were identified. Diet was assessed by a modified diet history method. A borderline interaction was observed between the α-linolenic acid (ALA) (18:3n-3)-to-linoleic acid (LA) (18:2n-6) intake ratio and FADS1 genotype on CVD incidence (P = 0.06). The ALA-to-LA intake ratio was inversely associated with CVD risk only among participants homozygous for the minor T-allele (HR for quintile 5 vs. quintile 1 = 0.72; 95% CI: 0.50, 1.04; P-trend = 0.049). When excluding participants reporting unstable food habits in the past (35%), the interaction between the ALA-to-LA intake ratio and FADS1 genotype on CVD incidence was strengthened and statistically significant (P = 0.04). Additionally, we observed a significant interaction between ALA and FADS1 genotype on ischemic stroke incidence (P = 0.03). ALA was inversely associated with ischemic stroke only among TT genotype carriers (HR for quintile 5 vs. quintile 1 = 0.50; 95% CI: 0.27, 0.94; P-trend = 0.02). In this large cohort, we found some weak, but not convincing, evidence of effect modification by genetic variation in FADS1 on the associations between PUFA intakes and CVD risk. For the 11% of the population homozygous for the minor T-allele of rs174546 that associates with lower ∆5 FADS activity, high ALA intake and ALA-to-LA intake ratio may be preferable in the prevention of CVD and ischemic stroke.

Topics: Adult; Aged; Alleles; alpha-Linolenic Acid; Cardiovascular Diseases; Delta-5 Fatty Acid Desaturase; Diet; Diet Surveys; Dietary Fats; Energy Intake; Fatty Acid Desaturases; Feeding Behavior; Female; Genotype; Humans; Linoleic Acid; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors; Stroke

Because alterations in blood fatty acid (FA) composition by dietary lipids are associated with insulin resistance and related metabolic disorders, we hypothesized that serum phospholipid FA composition would reflect the early alteration of fasting glycemic status, even in people without metabolic syndrome (MetS). To examine this hypothesis, serum phospholipid FA, desaturase activities, fasting glycemic status, and cardiometabolic parameters were measured in study participants (n = 1022; 30-69 years; male, n = 527; female, n = 495; nondiabetics without disease) who were stratified into normal fasting glucose (NFG) and impaired fasting glucose (IFG) groups. Total monounsaturated FA (MUFA), oleic acid (OA; 18:1n-9), dihomo-γ-linolenic acid (DGLA; 20:3n-6), Δ-9-desaturase activity (D9D; 18:1n-9/18:0), and DGLA/linoleic acid (20:3n-6/18:2n-6) in serum phospholipids were significantly higher in IFG subjects than NFG controls. Study subjects were subdivided into 4 groups, based on fasting glucose levels and MetS status. Palmitoleic acid (16:1n-7) was highest in IFG-MetS and lowest in NFG-non-MetS subjects. Oleic acid and D9D were higher in IFG-MetS than in the other 3 groups. Dihomo-γ-linolenic acid and DGLA/linoleic acid were higher in MetS than in non-MetS, regardless of fasting glucose levels. The high-sensitivity C-reactive proteins (hs-CRPs) and 8-epi-prostaglandin-F2α were higher in IFG than in NFG, regardless of MetS status. Oxidized low-density lipoproteins were higher in IFG-MetS than in the other 3 groups. Total MUFAs, OA, and D9D were positively correlated with homeostasis model assessment of insulin resistance, fasting glucose, triglyceride, hs-CRP, and 8-epi-prostaglandin-F2α. Palmitoleic acid was positively correlated with triglyceride and hs-CRP. Lastly, total MUFA, OA, palmitoleic acid, and D9D were associated with early alteration of fasting glycemic status, therefore suggesting that these may be useful markers for predicting the risk of type 2 diabetes and cardiometabolic diseases.

Topics: 8,11,14-Eicosatrienoic Acid; Biomarkers; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dinoprost; Fasting; Fatty Acids, Monounsaturated; Female; Humans; Insulin; Insulin Resistance; Linoleic Acid; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Oleic Acid; Phospholipids; Stearoyl-CoA Desaturase; Triglycerides

Dietary guidelines support intake of polyunsaturated fatty acids (PUFAs) in fish and vegetable oils. However, some controversy remains about benefits of PUFAs, and most prior studies have relied on self-reported dietary assessment in relatively homogeneous populations.. In a multiethnic cohort of 2837 US adults (whites, Hispanics, African Americans, Chinese Americans), plasma phospholipid PUFAs were measured at baseline (2000-2002) using gas chromatography and dietary PUFAs estimated using a food frequency questionnaire. Incident cardiovascular disease (CVD) events (including coronary heart disease and stroke; n=189) were prospectively identified through 2010 during 19 778 person-years of follow-up. In multivariable-adjusted Cox models, circulating n-3 eicosapentaenoic acid and docosahexaenoic acid were inversely associated with incident CVD, with extreme-quartile hazard ratios (95% CIs) of 0.49 for eicosapentaenoic acid (0.30 to 0.79; Ptrend=0.01) and 0.39 for docosahexaenoic acid (0.22 to 0.67; Ptrend<0.001). n-3 Docosapentaenoic acid (DPA) was inversely associated with CVD in whites and Chinese, but not in other race/ethnicities (P-interaction=0.01). No significant associations with CVD were observed for circulating n-3 alpha-linolenic acid or n-6 PUFA (linoleic acid, arachidonic acid). Associations with CVD of self-reported dietary PUFA were consistent with those of the PUFA biomarkers. All associations were similar across racial-ethnic groups, except those of docosapentaenoic acid.. Both dietary and circulating eicosapentaenoic acid and docosahexaenoic acid, but not alpha-linolenic acid or n-6 PUFA, were inversely associated with CVD incidence. These findings suggest that increased consumption of n-3 PUFA from seafood may prevent CVD development in a multiethnic population.

Topics: Aged; Aged, 80 and over; alpha-Linolenic Acid; Arachidonic Acid; Asian; Biomarkers; Black or African American; Cardiovascular Diseases; China; Chromatography, Gas; Cohort Studies; Diet; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Hispanic or Latino; Humans; Linoleic Acid; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Surveys and Questionnaires; United States; White People

Saturated and trans fatty acids have been associated with the risk to develop cardiovascular diseases. However, health-promoting effects are associated with consumption of anhydrous milk fat (AMF) and ruminant trans fatty acids, such as conjugated linoleic acid (CLA) and vaccenic acid (VA) contained in the lipid fraction of milk and dairy products. The purpose of this study was to evaluate the effect of AMF naturally enriched with CLA and VA in spontaneously hypertensive rats (SHR), using sterculic oil to inhibit the conversion of VA into CLA. The administration of AMF to SHR during 7 weeks exerted beneficial effects on cardiovascular risk biomarkers (reduction of insulin, blood lipids, increase of adiponectin). When sterculic oil was included, some parameters were further ameliorated (reduction of insulin, increase of adiponectin). Sterculic oil alone reduced body weight and adiposity, and improved blood pressure, adiponectin and triglyceride levels.

Topics: Adiponectin; Adiposity; Animals; Biomarkers; Blood Pressure; Cardiovascular Diseases; Cyclopropanes; Diet; Dietary Fats; Fatty Acids, Monounsaturated; Hypertension; Insulin; Linoleic Acid; Linoleic Acids, Conjugated; Lipids; Male; Milk; Oleic Acids; Rats; Rats, Inbred SHR; Ruminants; Triglycerides; Weight Loss

Hempseed is rich in polyunsaturated fatty acids (PUFAs), which have potential as therapeutic compounds for the treatment of neurodegenerative and cardiovascular disease. However, the effect of hempseed meal (HSM) intake on the animal models of these diseases has yet to be elucidated. In this study, we assessed the effects of the intake of HSM and PUFAs on oxidative stress, cytotoxicity and neurological phenotypes, and cholesterol uptake, using Drosophila models. HSM intake was shown to reduce H(2)O(2) toxicity markedly, indicating that HSM exerts a profound antioxidant effect. Meanwhile, intake of HSM, as well as linoleic or linolenic acids (major PUFA components of HSM) was shown to ameliorate Aβ42-induced eye degeneration, thus suggesting that these compounds exert a protective effect against Aβ42 cytotoxicity. On the contrary, locomotion and longevity in the Parkinson's disease model and eye degeneration in the Huntington's disease model were unaffected by HSM feeding. Additionally, intake of HSM or linoleic acid was shown to reduce cholesterol uptake significantly. Moreover, linoleic acid intake has been shown to delay pupariation, and cholesterol feeding rescued the linoleic acid-induced larval growth delay, thereby indicating that linoleic acid acts antagonistically with cholesterol during larval growth. In conclusion, our results indicate that HSM and linoleic acid exert inhibitory effects on both Aβ42 cytotoxicity and cholesterol uptake, and are potential candidates for the treatment of Alzheimer's disease and cardiovascular disease.

Topics: alpha-Linolenic Acid; Amyloid beta-Peptides; Animals; Animals, Genetically Modified; Antioxidants; Cannabis; Cardiovascular Diseases; Cholesterol; Compound Eye, Arthropod; Drosophila melanogaster; Hydrogen Peroxide; Hypercholesterolemia; Linoleic Acid; Lipid Metabolism; Motor Activity; Neurodegenerative Diseases; Peptide Fragments; Seeds

Topics: alpha-Linolenic Acid; Cardiovascular Diseases; Diet; Dietary Fats; Docosahexaenoic Acids; Eicosapentaenoic Acid; Energy Intake; Female; France; Guidelines as Topic; Humans; Linoleic Acid; Male; Nutrition Policy; Nutritional Physiological Phenomena; Nutritional Requirements; White People

Depression is associated with an increased risk of cardiovascular disease, but the association with dietary habits is not well understood. The aim of this work was to statistically model the association of depressive symptoms with fatty acids intake in persons free of cardiovascular disease.. A random multistage sampling, stratified by gender and age, was performed during 2001-2002. In the present work, psychological and dietary data from 453 men (19-89 years) and 400 women (18-84 years) were analyzed. Depression was assessed with the Zung's Self-rating Depression Scale (ZDRS). After a validation for the investigated population, plasma fatty acids in the form of their methyl esters were determined by gas chromatography, while dietary fatty acids were determined through a semiquantitative food frequency questionnaire and local food composition tables.. Women had significantly higher scores on the ZDRS as compared with men (47 ± 9 vs. 43 ± 10, p < 0.001). Multiadjusted data analysis after adjusting for age, gender, lifestyle, and dietary habits revealed that increased polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) concentrations, and, more specifically, high concentrations of plasma total n-3 fatty acids (b ± SE: -1.9 ± 0.5, p  =  0.03), docosahexaenoic acid (-2.91 ± 1.04, p  =  0.02), eicosapentaenoic acid (-2.54 ± 0.84, p  =  0.03), α-linoleic acid (-16.8 ± 7.3, p  =  0.01), and linoleic acid (-3.97 ± 0.21, p  =  0.03), were associated with lower scores in the depression scale used.. These results indicate that increased PUFA and MUFA concentrations are associated with diminished depressive symptomatology among apparently healthy adults.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cross-Sectional Studies; Depression; Docosahexaenoic Acids; Eicosapentaenoic Acid; Energy Intake; Fatty Acids, Monounsaturated; Feeding Behavior; Female; Greece; Humans; Life Style; Linear Models; Linoleic Acid; Male; Middle Aged; Psychiatric Status Rating Scales; Surveys and Questionnaires; Young Adult

Topics: Arachidonic Acid; Cardiovascular Diseases; Diet; Dietary Fats; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Humans; Linoleic Acid; Public Health

Investigations suggest a protective role of n-3 polyunsaturated fatty acids (PUFA) but opposing roles of n-6 PUFA in inflammation, but the effects in vivo the human are not clear. We therefore tested the hypothesis that higher intakes of n-3 PUFA and n-6 PUFA are associated with lower levels of inflammation among a population consuming a diet high in PUFA. This study aimed to assess the association between PUFA intake and serum C-reactive protein (CRP) concentrations in a group of Japanese employees. The study subjects were 300 men and 211 women aged 21 to 67 years working in 2 municipal offices of Japan. We measured the serum high-sensitivity CRP concentrations by the latex agglutination nephelometry method and assessed dietary habits by a validated self-administered diet history questionnaire. We analyzed the data using multiple linear regression analysis with adjustment for potential confounding variables. Mean serum CRP concentrations tended to decrease as the intake of eicosapentaenoic acid, docosahexaenoic acid, or their combination increased in men and women, although none of these relationships was statistically significant. In men, there were statistically significant inverse relationships between dietary intake of n-3 or n-6 PUFA and serum CRP concentrations (P for trend = .03 and .008, respectively). Among specific PUFA, only alpha-linolenic acid and linoleic acid showed clear inverse relationships (P for trend = .001 and .003, respectively) in men. The results suggest that increased intake of not only alpha-linolenic acid (n-3 PUFA) but also linoleic acid (n-6 PUFA) has a beneficial effect on systemic inflammation in men.

Topics: Adult; Age Factors; Aged; Alcoholic Beverages; alpha-Linolenic Acid; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Diet; Diet Surveys; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Inflammation; Japan; Linoleic Acid; Male; Middle Aged; Motor Activity; Multivariate Analysis; Selection Bias; Sex Characteristics; Smoking; Surveys and Questionnaires

Substitution of dietary polyunsaturated for saturated fat has long been recommended for the primary prevention of cardiovascular disease (CVD), but only a few prospective cohort studies have provided support for this advice.. We assessed the association of dietary linoleic and total polyunsaturated fatty acid (PUFA) intake with cardiovascular and overall mortality in a population-based cohort of 1551 middle-aged men. Dietary fat composition was estimated with a 4-day food record and serum fatty acid composition.. During the 15-year follow-up, 78 men died of CVD and 225 of any cause. Total fat intake was not related to CVD or overall mortality. Men with an energy-adjusted dietary intake of linoleic acid (relative risk [RR] 0.39; 95% confidence interval [CI], 0.21-0.71) and PUFA (RR, 0.38; 95% CI, 0.20-0.70) in the upper third were less likely to die of CVD than men with intake in the lower third after adjustment for age. Multivariate adjustment weakened the association somewhat. Mortality from CVD was also lower for men with proportions of serum esterified linoleic acid (RR, 0.42; 95% CI, 0.21-0.80) and PUFA (RR, 0.25; 95% CI, 0.12-0.50) in the upper vs lower third, with some attenuation in multivariate analyses. Serum and to a lesser extent dietary linoleic acid and PUFA were also inversely associated with overall mortality.. Dietary polyunsaturated and more specifically linoleic fatty acid intake may have a substantial cardioprotective benefit that is also reflected in overall mortality. Dietary fat quality seems more important than fat quantity in the reduction of cardiovascular mortality in men.

Topics: Adult; Age Distribution; Biomarkers; Cardiovascular Diseases; Cause of Death; Cohort Studies; Dietary Supplements; Fatty Acids, Unsaturated; Finland; Humans; Linoleic Acid; Male; Middle Aged; Primary Prevention; Probability; Proportional Hazards Models; Prospective Studies; Risk Assessment; Sensitivity and Specificity; Survival Analysis

This study describes the effect of substituting dietary linoleic acid (18:2 n-6) with alpha-linolenic acid (18:3 n-3) on sucrose-induced insulin resistance (IR). Wistar NIN male weanling rats were fed casein based diet containing 22 energy percent (en%) fat with approximately 6, 9 and 7 en% saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) respectively for 3 months. IR was induced by replacing starch (ST) with sucrose (SU). Blends of groundnut, palmolein, and linseed oil in different proportions furnished the following levels of 18:3 n-3 (g/100 g diet) and 18:2 n-6/18:3 n-3 ratios respectively: ST-220 (0.014, 220), SU-220 (0.014, 220), SU-50 (0.06, 50), SU-10 (0.27, 10) and SU-2 (1.1, 2). The results showed IR in the sucrose fed group (SU-220) as evidenced by increase in fasting plasma insulin and area under the curve (AUC) of insulin in response to oral glucose load. In SU-220, the increase in adipocyte plasma membrane cholesterol/phospholipid ratio was associated with a decrease in fluidity, insulin stimulated glucose transport, antilipolytic effect of insulin and increase in basal and norepinephrine stimulated lipolysis in adipocytes. In SU-50, sucrose induced alterations in adipocyte lipolysis and antilipolysis were normalized. However, in SU-2, partial corrections in plasma insulin, AUC of insulin and adipocyte insulin stimulated glucose transport were observed. Further, plasma triglycerides and cholesterol decreased in SU-2. In diaphragm phospholipids, the observed dose dependent increase in long chain (LC) n-3 PUFA was associated with a decrease in LC-n-6 PUFA but insulin stimulated glucose transport increased only in SU-2. Thus, this study shows that the substitution of one-third of dietary 18:2 n-6 with 18:3 n-3 (SU-2) results in lowered blood lipid levels and increases peripheral insulin sensitivity, possibly due to the resulting high LCn-3 PUFA levels in target tissues of insulin action. These findings suggest a role for 18:3 n-3 in the prevention of insulin resistant states. The current recommendation to increase 18:3 n-3 intake for reducing cardiovascular risk may also be beneficial for preventing IR in humans.

Topics: Adipocytes; alpha-Linolenic Acid; Animals; Biological Transport, Active; Blood Glucose; Cardiovascular Diseases; Cell Membrane; Diaphragm; Dietary Fats; Glucose; Insulin; Insulin Resistance; Linoleic Acid; Lipolysis; Male; Norepinephrine; Rats; Rats, Wistar; Sucrose

Vegetables and fruits have been shown to be good sources of antioxidants. Benincasa hispida (wax gourd) has been used in traditional Chinese medicine to treat hypertension and inflammation. The aims of this study were to investigate the abilities of antioxidation and inhibition of angiotensin-converting enzyme (ACE) activity of wax gourd pulp, core, seed, and peel prepared by different extraction methods. The fresh weights required to reach 50% inhibition of linoleic acid oxidation were higher in fresh extracts, compared to other extraction methods. Fresh weights required to reach 50% inhibition were the lowest in seed. The seed had the lowest Cu2+ -induced low-density lipoprotein (LDL) oxidation percentage and inhibition level of ACE activity among all parts. The higher antioxidant capacity of the seed may result from the higher total phenolics contents and superoxide dismutase activity. The abilities of antioxidation and ACE activity inhibition may provide protective effects against cardiovascular diseases and cancers.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Cardiovascular Diseases; Cucurbitaceae; Humans; Linoleic Acid; Lipoproteins, LDL; Neoplasms; Oxidation-Reduction; Phenols; Plant Extracts; Seeds; Superoxide Dismutase

We examined the effect of dietary manipulation of palmitic acid (20% [w/w] palm oil [PO]) on cardiomyocyte apoptosis in the rat heart under normoglycemic and hyperglycemic conditions in vivo. We used 20% (w/w) sunflower oil (SO; a diet rich in omega-6 polyunsaturated fatty acids) as an isocaloric control.. Adult male Wistar rats were fed experimental diets containing normal laboratory chow (5% corn oil) or a high fat diet (AIN-76A with PO or SO) for 4 wk. Subsequently, to induce diabetes, rats were injected with streptozotocin (55 mg/kg, intravenously). After 4 d of diabetes, hearts were tested for evidence of lipotoxicity and cell death, and the serum for its related markers.. Feeding PO and SO magnified palmitic and linoleic acid contents within lipoproteins and hearts respectively. Compared with SO, PO diabetic hearts demonstrated significantly higher levels of apoptosis, with an altered Bax:Bcl-2 ratio, augmented lipid peroxidation, and protein modification by formation of nitrotyrosine. Interestingly, SO-fed diabetic animals demonstrated an increase in serum lactate dehydrogenase and myocardial necrotic changes.. In marked contrast to results obtained in vitro, PO feeding led to only a minor fraction of cardiomyocytes undergoing apoptosis and suggests that, in the intact heart, protective mechanisms could be triggered that dampen excessive apoptosis. Of greater clinical significance was the observation that "heart-friendly" vegetable oils such as SO, rich in omega-6 polyunsaturated fatty acids, could precipitate cardiac necrosis, and questions its beneficial role in the cardiovascular system, especially following diabetes.

Topics: Animals; Apoptosis; Cardiovascular Diseases; Diabetes Mellitus, Experimental; Dietary Fats, Unsaturated; Hyperglycemia; Linoleic Acid; Male; Myocytes, Cardiac; Palm Oil; Palmitic Acid; Plant Oils; Rats; Rats, Wistar; Sunflower Oil

Topics: Animals; Cardiovascular Diseases; Consumer Advocacy; Fatty Acids; Food Labeling; Humans; Isomerism; Linoleic Acid; Risk Factors

To examine dietary fat and meat intake in relation to risk of type 2 diabetes.. We prospectively followed 42,504 male participants of the Health Professionals Follow-Up Study who were aged 40-75 years and free of diagnosed diabetes, cardiovascular disease, and cancer in 1986. Diet was assessed by a validated food frequency questionnaire and updated in 1990 and 1994. During 12 years of follow-up, we ascertained 1,321 incident cases of type 2 diabetes.. Intakes of total fat (multivariate RR for extreme quintiles 1.27, CI 1.04-1.55, P for trend=0.02) and saturated fat (1.34, 1.09-1.66, P for trend=0.01) were associated with a higher risk of type 2 diabetes. However, these associations disappeared after additional adjustment for BMI (total fat RR 0.97, CI 0.79-1.18; saturated fat 0.97, 0.79-1.20). Intakes of oleic acid, trans-fat, long-chain n-3 fat, and alpha-linolenic acid were not associated with diabetes risk after multivariate adjustment. Linoleic acid was associated with a lower risk of type 2 diabetes in men <65 years of age (RR 0.74, CI 0.60-0.92, P for trend=0.01) and in men with a BMI <25 kg/m(2) (0.53, 0.33-0.85, P for trend=0.006) but not in older and obese men. Frequent consumption of processed meat was associated with a higher risk for type 2 diabetes (RR 1.46, CI 1.14-1.86 for > or = 5/week vs. <1/month, P for trend <0.0001).. Total and saturated fat intake were associated with a higher risk of type 2 diabetes, but these associations were not independent of BMI. Frequent consumption of processed meats may increase risk of type 2 diabetes.

Topics: Adult; Age Factors; Aged; Body Mass Index; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Fats; Dietary Proteins; Humans; Hypercholesterolemia; Hypertension; Incidence; Linoleic Acid; Male; Meat; Middle Aged; Prospective Studies; Risk Factors; Smoking; Surveys and Questionnaires

Coronary heart disease (CHD) risk is positively linked with dietary saturates and negatively linked with polyunsaturated fatty acids (PUFAs). Consumption of omega-3 fatty acids, such as in fish, appears highly protective against CHD. PUFAs (linoleic acid or omega-6) lower low-density lipoprotein (LDL) cholesterol levels most, and saturates, especially butter fat, raise LDL levels most. Fish oil fatty acids (omega-3) lower triglyceride and raise high-density lipoprotein (HDL) cholesterol levels. A higher ratio of dietary omega-3 to omega-6 fatty acids than is currently consumed in our population may be desirable, and can be achieved by increasing consumption of fish and alpha-linolenic acid in canola, soy and flaxseed oils. Large prospective trials show that people who experience least CHD have a pattern of eating that is rich in fish, PUFAs, whole-grain cereals, fruits and vegetables and low-fat dairy foods, and low in saturates from dairy fat, meat fat and fried foods.

Topics: Adult; Cardiovascular Diseases; Dietary Fats; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Humans; Linoleic Acid; Lipids

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Fats; Dietary Fats, Unsaturated; Fatty Acids; Humans; Linoleic Acid; Oleic Acid; Risk Factors

Since cholesterol was discovered in atherosclerotic plaques and was able, when given in diet, to induce the same type of lesions in animals, the aim of previous dietary changes was to reduce serum cholesterol as much as possible. For this purpose, the intake of saturated fats was decreased and replaced by linoleic acid, the main fatty acid lowering cholesterol. Nevertheless, this type of diet in primary or secondary prevention did not succeed in reducing satisfactorily cardiovascular and total mortality unless the intake of fish (DART and Hjermann trials) i.e. of n-3 fatty acids, was increased. On the other hand, the diet with the greatest life expectancy in the western world is that of Crete, largely vegetarian with a high intake of alpha-linolenic acid. Such a diet, compared to the usual prudent diet in 600 patients after a first myocardial infarction, reduced within a few months all cause mortality and cardiovascular events by more than 70%. Thus a highly palatable diet adapted from Crete seems to be much more efficient to prevent recurrences and death after a first myocardial infarction than the hypocholesterolemic diet presently advised.

Topics: Animals; Cardiovascular Diseases; Cholesterol; Clinical Trials as Topic; Diet; Dietary Fats; Greece; Humans; Linoleic Acid; Multicenter Studies as Topic; Platelet Aggregation

We investigated the relationship between assessment of fatty acid intake by a 3-day food record and by capillary gas chromatography of erythrocyte phospholipid fatty acid. The study was performed in a sample of 244 men aged 45 to 66 years from the general population who were participating in the Monitoring of Cardiovascular Disease (MONICA)-Lille survey. The relationship between each nutrient and food item and erythrocyte phospholipid fatty acid was investigated by a regression model on proportion including each food item and nutrient as a dependent variable and percentage of fatty acid and covariables (nonalcoholic energy intake, age, alcohol intake, and smoking) as independent variables. Polyunsaturated fat and linoleic acid intake were positively correlated with linoleic acid content of erythrocytes (beta = 0.641 and 0.604, respectively, P < .001). Monounsaturated and saturated fat intake were correlated with oleic acid (beta = 0.375 and 0.373, respectively, P < .01). Fish intake correlated positively with docosahexaenoic acid (DHA) (beta = 0.383, P < .001) and negatively with arachidonic acid (beta = -0.509, P < .01). These data confirm, on a group level, a good relationship between assessment of polyunsaturated fat intake by a 3-day record and linoleic acid content of erythrocyte membranes. These data suggest that erythrocyte oleic acid content is a marker of both saturated and monounsaturated fat intake.

Topics: Animals; Arachidonic Acid; Cardiovascular Diseases; Diet Records; Dietary Fats; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Erythrocytes; Fatty Acids; Fishes; Food; Humans; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Oleic Acid; Oleic Acids; Phospholipids

Linoleic acid in serum total lipids was the first variable in the stepwise regression analysis of metabolic, nutritional and cardiovascular factors in a secondary preventive study of postinfarction middle-aged men. It was followed in the regression analysis where the dependent variable was cardiovascular death by previous myocardial infarction, heart volume index and hyperlipoproteinaemia. Linoleic acid was the only fatty acid entering the regression. Unlike other fatty acids, it exhibited by its low percentage an accumulation of deaths. The decreased percentage of linoleic acid was also evident in the comparison of fatty acid patterns of cardiovascular deaths to age- and triglyceride-matched men free from ischaemic heart disease. This study confirms prospective associations found in previously healthy men. Conclusions are drawn about the relevance of low serum linoleic acid to long term prognosis after MI.

Topics: Cardiovascular Diseases; Czechoslovakia; Dietary Fats; Energy Intake; Fatty Acids; Humans; Hyperlipoproteinemias; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Myocardial Infarction; Myocardium; Prognosis