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The Ratio of Omega-6/Omega-3 Fatty Acid: Implications and Application as a Marker to Diabetes
Abstract
Omega-3 and omega-6 groups of polyunsaturated fatty acids (PUFA) are non-interconvertible and metabolically and functionally different, with key opposing metabolic activities in human physiology. The PUFA content of the cell membrane is mostly determined by dietary intake. They are a component of the cellular membrane, improving its fluidity and PUFAs must be released from the membrane by phospholipases in order for signal transmission to occur. Long-chain polyunsaturated fatty acids exert their anti-inflammatory effects by inhibiting lipogenesis and increasing the production of resolvins and protectins. n-3 PUFAs mediate some of these effects by antagonizing n-6 PUFA-induced proinflammatory prostaglandin E formation. Today’s industrialized societies with Westernized diet styles have higher overall energy intake, and n-6 PUFAs, but lower energy expenditure. Omega-3 PUFA attenuates ER stress and increases mitochondrial fatty acid β-oxidation and mitochondrial uncoupling. There is competition between omega-3 fatty acids and omega-6 for desaturation enzymes. The unbalanced omega 6/omega 3 ratio in favor of omega 6 PUFAs contributes to the prevalence of atherosclerosis, obesity, and diabetes. n-3 PUFAs are considered to be more protective against inflammation compared with omega 6 PUFA, suggesting the importance of maintaining an ideal balance.
... u-3 PUFAs and their beneficial health effects u-3 PUFAs are abundant natural nutritional compounds with long carbon chains and at least two double bonds [30,31]. These fatty acids have carbon chain lengths comprised of 18e22 carbon atoms, and the term u-3 indicates the location of the first double bond between the third and the fourth carbon atoms counting from the terminal methyl group [32]. Among these fatty acids, alinolenic acid (ALA; 18:3 n-3), eicosapentaenoic acid (EPA; 20:5 n-3), and docosahexaenoic acid (DHA; 22:6 n-3) are most commonly investigated [33]. ...
Lyotropic non-lamellar liquid crystalline (LLC) nano-self-assemblies (including cubosomes and hexosomes) are attractive versatile platforms for encapsulation and delivery of drugs and nutritional molecules. This is due to their unique structural features and architectural arrangements that afford loading of small molecules and macromolecules having different physicochemical properties with high efficiency. Considering the reported health promoting effects of long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and their precursors ω-3 PUFA monoacylglycerols, here we focus on physicochemical and biological properties of
a new family of non-lamellar LLC nanoparticles assembled either from binary mixtures of phosphatidylglycerol and three types of ω-3 PUFAs, or from single ω-3 PUFA monoacylglycerols. We discuss recent progress in understanding their complexity, pH sensitivity, and structural tunability, and highlight their potential applications in health and medicine.
... It is required by pregnant women for proper growth and development of the fetus, brain development in children, prevention of non-communicable diseases in adults, and mental health of the elderly person (Ruxto 2004). Omega-3 fatty acids are beneficial against several diseases such as cardiovascular diseases, dementia, neurodegenerative diseases, diabetes, depression, and some types of cancer (Shahidi and Ambigaipalan 2018;de Branco et al. 2023;Shetty, Kumari, and Varadarajan 2023) (Figure 1). Omega-3 fatty acids gained importance to fight against the global pandemic, i.e., COVID-19 as they prevent cytokine storms raised due to inflammatory response of the body (Hathaway et al. 2020). ...
Omega-3 fatty acids have gained attention due to numerous health benefits. Eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) are long chain omega-3 fatty acids produced from precursor ALA (α-linolenic acid) in humans but their rate of biosynthesis is low, therefore, these must be present in diet or should be taken as supplements. The commercial sources of omega-3 fatty acids are limited to vegetable oils and marine sources. The rising concern about vegan source, fish aquaculture conservation and heavy metal contamination in fish has led to the search for their alternative source. Microalgae have gained importance due to the production of high-value EPA and DHA and can thus serve as a sustainable and promising source of long chain omega-3 fatty acids. Although the bottleneck lies in the optimization for enhanced production that involves strategies viz. strain selection, optimization of cultivation conditions, media, metabolic and genetic engineering approaches; while co-cultivation, use of nanoparticles and strategic blending have emerged as innovative approaches that have made microalgae as potential candidates for EPA and DHA production. This review highlights the possible strategies for the enhancement of EPA and DHA production in microalgae. This will pave the way for their large-scale production for human health benefits.
Most of the edible vegetable oils in southern Kaduna are locally processed and are available in a large commercial quantity with little known about their fatty acid (FA) content. The aim of this work was to investigate the fatty acid content of these oils and their potential impact on human health. Six commonly used edible vegetable oil samples sold in various Southern Kaduna markets were analyzed for different fatty acids content using gas chromatography-mass spectrometry (GC-MS). The result of the analysis showed differences in the contents of saturated fatty acids (SFAs), monounsaturated (MUFAs), and polyunsaturated (PUFAs). Coconut oil and kernel oil showed high content of SFAs (86.21% and 78.76%) respectively, while olive oil and peanut oil displayed significant amounts of MUFAs (75.40% and 47.62%) respectively due to high content of oleic acid (C18:1). Soybean oil with 58.06% of linoleic acid (C18:2) showed the highest total PUFA content of 65.23%. The Health Risk Index (HRI) was evaluated to assessed the impact associated with the overall intake of fatty acids in vegetable oils. The HRI were 1.78 (peanut), 0.04 (kernel), 0.23 (palm), 0.2(coconut), 4.05(soybean) and olive (0.71). Thus, soybean oil, peanut oil and olive oil have the optimum PUFA:SFA ratio according to FAO/WHO recommendations. Hence, they are recommended for mass consumption. The health promotion index (HPI) was also evaluated to assessed the content of certain essential fatty acids in various oils which have specific health benefits. The results of HPI investigation showed that only Soybean oil contains the balanced ω-6: ω-3 fatty acid ratio of 8.1 than others.
Polyunsaturated fatty acids (PUFAs) contain ≥2 double-bond desaturations within the acyl chain. Omega-3 (n-3) and Omega-6 (n-6) PUFAs are the two known important families in human health and nutrition. In both Omega families, many forms of PUFAs exist: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) from the n-3 family and linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA) from the n-6 family are the important PUFAs for human health. Omega-3 and Omega-6 PUFAs are competitively metabolized by the same set of desaturation, elongation, and oxygenase enzymes. The lipid mediators produced from their oxidative metabolism perform opposing (antagonistic) functions in the human body. Except for DGLA, n-6 PUFA-derived lipid mediators enhance inflammation, platelet aggregation, and vasoconstriction, while those of n-3 inhibit inflammation and platelet aggregation and enhance vasodilation. Overconsumption of n-6 PUFAs with low intake of n-3 PUFAs is highly associated with the pathogenesis of many modern diet-related chronic diseases. The volume of n-6 PUFAs is largely exceeding the volume of n-3PUFAs. The current n-6/n-3 ratio is 20-50/1. Due to higher ratios of n-6/n-3 in modern diets, larger quantities of LA- and AA-derived lipid mediators are produced, becoming the main causes of the formation of thrombus and atheroma, the allergic and inflammatory disorders, and the proliferation of cells, as well as the hyperactive endocannabinoid system. Therefore, in order to reduce all of these risks which are due to overconsumption of n-6 PUFAs, individuals are required to take both PUFAs in the highly recommended n-6/n-3 ratio which is 4-5/1.
Type 1 diabetes mellitus is an autoimmune disease characterized by increased production of pro-inflammatory cytokines secreted by infiltrating macrophages and T cells that destroy pancreatic β cells in a free radical-dependent manner that causes decrease or absence of insulin secretion and consequent hyperglycemia. Hence, suppression of pro-inflammatory cytokines and oxidative stress may ameliorate or decrease the severity of diabetes mellitus. To investigate the effect and mechanism(s) of action of RVD1, an anti-inflammatory metabolite derived from docosahexaenoic acid (DHA), on STZ-induced type 1 DM in male Wistar rats, type 1 diabetes was induced by single intraperitoneal (i.p) streptozotocin (STZ-65 mg/kg) injection. RVD1 (60 ng/mL, given intraperitoneally) was administered from day 1 along with STZ for five consecutive days. Plasma glucose, IL-6, TNF-α, BDNF (brain-derived neurotrophic factor that has anti-diabetic actions), LXA4 (lipoxin A4), and RVD1 levels and BDNF concentrations in the pancreas, liver, and brain tissues were measured. Apoptotic (Bcl2/Bax), inflammatory (COX-1/COX-2/Nf-κb/iNOS/PPAR-γ) genes and downstream insulin signaling proteins (Gsk-3β/Foxo1) were measured in the pancreatic tissue along with concentrations of various antioxidants and lipid peroxides. RVD1 decreased severity of STZ-induced type 1 DM by restoring altered plasma levels of TNF-α, IL-6, and BDNF (p < 0.001); expression of pancreatic COX-1/COX-2/PPAR-γ genes and downstream insulin signaling proteins (Gsk-3β/Foxo1) and the concentrations of antioxidants and lipid peroxides to near normal. RVD1 treatment restored expression of Bcl2/Pdx genes, plasma LXA4 (p < 0.001) and RVD1 levels and increased brain, pancreatic, intestine, and liver BDNF levels to near normal. The results of the present study suggest that RVD1 can prevent STZ-induced type 1 diabetes by its anti-apoptotic, anti-inflammatory, and antioxidant actions and by activating the Pdx gene that is needed for pancreatic β cell proliferation.
Background:
Current evidence on the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance is inconsistent. Therefore, the aim is to explore the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in the U.S. noninstitutionalized population of older adults.
Methods:
We used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Intakes of ω-3 and ω-6 fatty acids were obtained through two 24-h dietary recalls and were adjusted by energy. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer's disease (CERAD) Word Learning sub-test, Animal Fluency test and Digit Symbol Substitution Test (DSST). For each cognitive test, people who scored lower than the lowest quartile in each age group were defined as having low cognitive performance. Binary logistic regression and restricted cubic spline models were applied to evaluate the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance.
Results:
A total of 2496 participants aged 60 years or older were included. In the full-adjusted model, the odds ratios (ORs) with 95% confidence interval (CI) of CERAD test score, Animal Fluency test score and DSST test score were 0.58 (0.38-0.88), 0.68 (0.47-0.99) and 0.59 (0.37-0.92) for the highest versus lowest tertile of dietary ω-3 fatty acids intake, respectively; the ORs with 95% CI of CERAD test score, Animal Fluency test score and DSST test score were 0.48 (0.31-0.75), 0.60 (0.40-0.92) and 0.50 (0.34-0.75) for the highest versus lowest tertile of dietary ω-6 fatty acids intake, respectively. The association between ω-6: ω-3 ratio and cognitive performance was not statistically significant in three tests. In dose-response relationship analysis, L-shaped associations were apparent for ω-3 and ω-6 fatty acids intake with CERAD test score, Animal Fluency test score and DSST test score.
Conclusions:
Dietary ω-3 and ω-6 fatty acids intake might be inversely associated with low cognitive performance.
Omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) are nowadays desirable components of oils with special dietary and functional properties. Their therapeutic and health-promoting effects have already been established in various chronic inflammatory and autoimmune diseases through various mechanisms, including modifications in cell membrane lipid composition, gene expression, cellular metabolism, and signal transduction. The application of ω-3 and ω-6 PUFAs in most common skin diseases has been examined in numerous studies, but their results and conclusions were mostly opposing and inconclusive. It seems that combined ω-6, gamma-linolenic acid (GLA), and ω-3 long-chain PUFAs supplementation exhibits the highest potential in diminishing inflammatory processes, which could be beneficial for the management of inflammatory skin diseases, such as atopic dermatitis, psoriasis, and acne. Due to significant population and individually-based genetic variations that impact PUFAs metabolism and associated metabolites, gene expression, and subsequent inflammatory responses, at this point, we could not recommend strict dietary and supplementation strategies for disease prevention and treatment that will be appropriate for all. Well-balanced nutrition and additional anti-inflammatory PUFA-based supplementation should be encouraged in a targeted manner for individuals in need to provide better management of skin diseases but, most importantly, to maintain and improve overall skin health.
A common feature of cancer cells is their ability to rewire their metabolism to sustain the production of ATP and macromolecules needed for cell growth, division and survival. In particular, the importance of altered fatty acid metabolism in cancer has received renewed interest as, aside their principal role as structural components of the membrane matrix, they are important secondary messengers, and can also serve as fuel sources for energy production. In this review, we will examine the mechanisms through which cancer cells rewire their fatty acid metabolism with a focus on four main areas of research. (1) The role of de novo synthesis and exogenous uptake in the cellular pool of fatty acids. (2) The mechanisms through which molecular heterogeneity and oncogenic signal transduction pathways, such as PI3K–AKT–mTOR signalling, regulate fatty acid metabolism. (3) The role of fatty acids as essential mediators of cancer progression and metastasis, through remodelling of the tumour microenvironment. (4) Therapeutic strategies and considerations for successfully targeting fatty acid metabolism in cancer. Further research focusing on the complex interplay between oncogenic signalling and dysregulated fatty acid metabolism holds great promise to uncover novel metabolic vulnerabilities and improve the efficacy of targeted therapies.
The recognition of ω-3 polyunsaturated acids (PUFAs) as essential fatty acids to normal growth and health was realized more than 80 years ago. However, the awareness of the long-term nutritional intake of ω-3 PUFAs in lowering the risk of a variety of chronic human diseases has grown exponentially only since the 1980s (1, 2). Despite the overwhelming epidemiological evidence, many attempts of using fish-oil supplementation to intervene human diseases have generated conflicting and often ambiguous outcomes; null or weak supporting conclusions were sometimes derived in the subsequent META analysis. Different dosages, as well as the sources of fish-oil, may have contributed to the conflicting outcomes of intervention carried out at different clinics. However, over the past decade, mounting evidence generated from genetic mouse models and clinical studies has shed new light on the functions and the underlying mechanisms of ω-3 PUFAs and their metabolites in the prevention and treatment of rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and type 1 diabetes. In this review, we have summarized the current understanding of the effects as well as the underlying mechanisms of ω-3 PUFAs on autoimmune diseases.
Over the past three decades, studies of essential biomolecules, long-chain polyunsaturated fatty acids of the omega-3 family (LC-PUFAs), namely eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have made considerable progress, resulting in several important assumptions. However, new data, which continue to appear, challenge these assumptions. Based on the current literature, an attempt is made to reconsider the following assumptions: 1. There are algal classes of high and low nutritive quality. 2. EPA and DHA decrease with increasing eutrophication in aquatic ecosystems. 3. Animals need EPA and DHA. 4. Fish are the main food source of EPA and DHA for humans. 5. Culinary treatment decreases EPA and DHA in products. As demonstrated, some of the above assumptions need to be substantially specified and changed.
Introduction
Cognitive impairment is a common consequence of epilepsy in children. This study aimed to assess the ratio of omega-6 to omega-3 fatty acid levels and its impact on cognitive function in children with idiopathic epilepsy.
Patients and methods
We performed a case-control study in 30 children with idiopathic epilepsy and 20 healthy children. We measured levels of alpha-linolenic acid (omega-3) and linoleic acid (omega-6) by means of gas-liquid chromatography. We assessed cognitive function with the Arabic version of the fourth edition of the Stanford-Binet test and the P300 component of event-related potentials. All children had an intelligent quotient greater than 70.
Results
Children with epilepsy had lower levels of omega-3 and higher levels of omega-6 fatty acids and an abnormal omega-6/omega-3 ratio compared to non-epileptic children. We found a significant positive correlation of serum omega-3 levels and a significant negative correlation of serum omega-6 levels with cognitive function scores and P300 latency in children with epilepsy.
Conclusion
Children with epilepsy have abnormal ratios of omega-6 to omega-3 fatty acid serum levels, which is associated with impaired cognitive function in these children.
Recent studies have highlighted the potential protective role of omega-3 polyunsaturated fatty acids (n-3 PUFA) in asthma. This study aimed at determining the association between seafood intake, serum PUFA composition and clinical endpoints of asthma in adults. A cross-sectional study of 642 subjects used the European Committee Respiratory Health Survey (ECRHS) questionnaire, skin prick tests, spirometry and methacholine challenge tests following ATS guidelines. Sera was analysed for n-3 and n-6 PUFA composition. Subjects had a mean age of 34 years, were largely female (65%) and 51% were current smokers. While 99% reported fish consumption, rock lobster, mussels, squid and abalone were also consumed less frequently. The prevalence of asthma symptoms was 11%, current asthma (ECRHS definition) was 8% and non-specific bronchial hyperresponsiveness (NSBH) was much higher (26%) In adjusted models the n-3 PUFAs 20:5 (EPA) and 22:5 (DPA) were significantly associated with a decreased risk of having NSBH. Total n-3 PUFA composition was associated with decreased NSBH risk (OR = 0.92), while high n-6 PUFA composition was associated with an increased risk (OR = 1.14).
Cardiovascular diseases are described as the leading cause of morbidity and mortality in modern societies. Therefore, the importance of cardiovascular diseases prevention is widely reflected in the increasing number of reports on the topic among the key scientific research efforts of the recent period. The importance of essential fatty acids (EFAs) has been recognized in the fields of cardiac science and cardiac medicine, with the significant effects of various fatty acids having been confirmed by experimental studies. Polyunsaturated fatty acids are considered to be important versatile mediators for improving and maintaining human health over the entire lifespan, however, only the cardiac effect has been extensively documented. Recently, it has been shown that omega-3 fatty acids may play a beneficial role in several human pathologies, such as obesity and diabetes mellitus type 2, and are also associated with a reduced incidence of stroke and atherosclerosis, and decreased incidence of cardiovascular diseases. A reasonable diet and wise supplementation of omega-3 EFAs are essential in the prevention and treatment of cardiovascular diseases prevention and treatment.
Background: The type 2 diabetes is one of the most common autoimmune diseases. Due to a key role in the metabolism of unsaturated fatty acids such as arachidonic acid, one of the most important precursors of immunity mediators, fatty acid desaturase (FADS) genes could have an important impact in the development of type 2 diabetes. Materials and
Methods: This study aimed to determine the relationship between polymorphisms rs174537 in FADS1 gene and rs174575 in FADS2 gene with type 2 diabetes in Iranian population. After extracting genomic DNA, the locations of mutations and allele types were identified with high‑resolution melting (HRM)‑polymerase chain reaction method. Then, association between these mutations with metabolic syndrome, dyslipidemia, and type 2 diabetes was investigated using χ2 correlation coefficients for variables and logistic regression.
Results: The results showed that among 50 diabetic participants, 68% of patients have the mutant allele for rs174537 in FADS1 gene. This rate is 26% for rs174575 in FADS2 gene. Based on the results, it seems that participants having rs174537 mutant allele are more prone to become diabetic but it has a beneficial effect on total and low‑density lipoprotein cholesterol and participants having rs174575 mutant are less prone to become diabetic, and also, it leads to higher triglycerides and body mass index (obesity).
Conclusions: Detecting FADS1 and FADS2, gene polymorphisms using HRM can be an anticipating tool for making decision on initiating lifestyle modifications to prevent type 2 diabetes.
Keywords: Fatty acid desaturase gene, polymorphism, type 2 diabetic
Objective To clarify the associations between serum omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acid (PUFA) levels and obesity-related metabolic abnormalities in patients with type 2 diabetes.
Materials and Methods Data from 225 Japanese patients with type 2 diabetes were cross-sectionally analyzed. The serum levels of n-6 PUFAs [dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) ] and n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) were measured, and the estimated Δ-5 desaturase (D5D) activity was calculated based on the AA to DGLA ratio. The associations between the composition of PUFAs and obesity-related parameters, including the body mass index (BMI), waist circumference, alanine amino transferase (ALT) level, homeostatic model assessment of insulin resistance (HOMA-IR), and body fat percentage, as measured by a bioelectrical impedance analysis, were analyzed.
Results Among the PUFAs, the DGLA level had the strongest correlations with BMI (p <0.001), waist circumference (p <0.001), ALT level (p <0.001), HOMA-IR (p <0.001), and body fat percentage (p <0.01). AA was positively correlated and D5D was negatively correlated with several obesity-related parameters, while n-3 PUFAs did not have a constant correlation. A multivariate regression analysis revealed that the DGLA level was an independent determinant for HOMA-IR (β = 0.195, p = 0.0066) after adjusting for sex, age, BMI, and the ALT, triglyceride, and HbA1c levels.
Conclusion A high serum DGLA level was associated with obesity, body fat accumulation, a high ALT level, and insulin resistance in patients with type 2 diabetes. The measurement of the serum PUFA levels may be useful for evaluating metabolic abnormalities and estimating the dietary habits of patients.
Background:
In this study, we investigated the associations of erythrocytes fatty acid composition, activities of delta-5 desaturase (D5D) and delta-6 desaturase (D6D), and other metabolic risk factors, with type 2 diabetes (T2D) risk to determine if rs174583 polymorphism of FADS2 gene had any effect on these associations.
Materials and methods:
Fatty acid profile of erythrocytes was determined using gas chromatography-mass spectrometry in 95 T2D patients and 95 apparently healthy participants. The genotypes of single-nucleotide polymorphism (SNP) of FADS2 gene were determined using the polymerase chain reaction-restriction fragment length polymorphism technique. Other biochemical parameters were measured in the serum using standard analytical procedures.
Results:
D6D activity was increased (P < 0.001) and D5D activity was decreased in T2D patients (P < 0.001) compared to controls. Homeostatic model assessment insulin resistance (HOMA-IR) index was positively correlated with D6D (r = 0.34, P < 0.001) and negatively correlated with D5D (r = -0.19, P = 0.02). Palmitic acid (P < 0.001) and dihomo-gamma-linolenic acid (P = 0.03) were higher and linoleic acid (P < 0.001) and arachidonic acid (AA) (P < 0.001) were lower in T2D patients. The distribution of rs174583 genotypes which includes C/T, C/C, and T/T was not different in the two groups (P = 0.63).
Conclusion:
In the population studied, there was a strong association in the erythrocytes fatty acid composition, D5D and D6D activities and other metabolic risk factors between non-T2D and T2D patients. In addition, there was a strong association in erythrocytes DGLA and AA contents and D5D activities between rs174583 genotypes in all participants. However, the distribution of rs174583 genotypes did not differ significantly between T2D patient and controls, and it did not appear to be an association between rs174583 SNP and incident of T2D.
Mitochondrial dysfunction and endoplasmic reticulum (ER) stress have been suggested to play a key role in insulin resistance development. Reactive oxygen species (ROS) production and lipid accumulation due to mitochondrial dysfunction seemed to be important mechanisms leading to cellular insulin resistance. Moreover, mitochondria are functionally and structurally linked to ER, which undergoes stress in conditions of chronic overnutrition, activating the unfolded protein response, which in turn activates the principal inflammatory pathways that impair insulin action. Among the nutrients, dietary fats are believed to play key roles in insulin resistance onset. However, not all dietary fats exert the same effects on cellular energy metabolism. Dietary omega 3 polyunsaturated fatty acids (PUFA) have been suggested to counteract insulin resistance development by modulating mitochondrial bioenergetics and ER stress. In the current review, we summarized current knowledge on the role played by mitochondrial and ER stress in inflammation and insulin resistance onset, focusing on the modulation role of omega 3 PUFA on these stress pathways. Understanding the mechanisms by which omega 3 PUFA modulates cellular metabolism and insulin resistance in peripheral tissues may provide additional details on the potential impact of omega 3 PUFA on metabolic function and the management of insulin resistance in humans.
The importance of dietary polyunsaturated fatty acids for our health and our economy is immense. The present paper is a quick guide to this topic, which is highly complex and full of conflicts. One aspect is highlighted, namely the relationship between these substances and our mental health. Relevant chemical and physical properties of polyunsaturated fatty acids are briefly presented. The questions of needs and supplies are discussed. The effects of these fatty acids on the human body, in particular the brain, are described. How do they influence mental health? The most recent meta-analyses and systematic reviews have been used as sources, and outstanding references have been selected. We want to convey updated knowledge, based on good science, for better decision making in preventive and therapeutic health care, as well as in agriculture, fishery and food industries.
Objective:
Evidence from several cross-sectional studies indicates that an increase in omega-6 to omega-3 fatty acids (FAs) may negatively affect cognition in old age. The hippocampus is among the first neural structures affected by age and atrophy in this brain region is associated with cognitive decline. Therefore, we hypothesized that a lower omega-6:3 FA ratio would predict better hippocampus-dependent spatial memory, and a higher general cognitive status.
Method:
Fifty-two healthy older adults completed a Food Frequency Questionnaire, the Montreal Cognitive Assessment test (MoCA; a test of global cognition) and virtual navigation tasks that assess navigational strategies and spatial memory.
Results:
In this cross-sectional study, a lower ratio of omega-6 to omega-3 FA intake strongly predicted more accurate hippocampus-dependent spatial memory and faster learning on our virtual navigation tasks, as well as higher cognitive status overall.
Conclusions:
These results may help elucidate why certain dietary patterns with a lower omega-6:3 FA ratio, like the Mediterranean diet, are associated with reduced risk of cognitive decline. (PsycINFO Database Record
Lipids encompass a wide variety of molecules such as fatty acids, sterols, phospholipids and triglycerides. These molecules represent a highly efficient energy resource and can act as structural elements of membranes, or as signaling molecules that regulate metabolic homeostasis through many mechanisms. Cells possess an integrated set of response systems to adapt to stresses such as those imposed by nutrient fluctuations during feeding-fasting cycles. While lipids are pivotal for these homeostatic processes, they can also contribute to detrimental metabolic outcomes. When metabolic stress becomes chronic and adaptive mechanisms are overwhelmed, as occurs during prolonged nutrient excess or obesity, lipid influx can exceed the adipose tissue storage capacity, and result in accumulation of harmful lipid species at ectopic sites such as liver and muscle. As lipid metabolism and immune responses are highly integrated, accumulation of harmful lipids or signaling intermediates can interfere with immune regulation in multiple tissues, causing a vicious cycle of immune-metabolic dysregulation. In this review, we summarize the role of lipotoxicity in metabolic inflammation at the molecular and tissue level, describe the significance of anti-inflammatory lipids in metabolic homeostasis, and discuss the potential of therapeutic approaches targeting pathways at the intersection of lipid metabolism and immune function.
In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity.
Docosahexaenoic acid (DHA) is the predominant omega-3 (n-3) polyunsaturated fatty acid (PUFA) found in the brain and can affect neurological function by modulating signal transduction pathways, neurotransmission, neurogenesis, myelination, membrane receptor function, synaptic plasticity, neuroinflammation, membrane integrity and membrane organization. DHA is rapidly accumulated in the brain during gestation and early infancy, and the availability of DHA via transfer from maternal stores impacts the degree of DHA incorporation into neural tissues. The consumption of DHA leads to many positive physiological and behavioral effects, including those on cognition. Advanced cognitive function is uniquely human, and the optimal development and aging of cognitive abilities has profound impacts on quality of life, productivity, and advancement of society in general. However, the modern diet typically lacks appreciable amounts of DHA. Therefore, in modern populations, maintaining optimal levels of DHA in the brain throughout the lifespan likely requires obtaining preformed DHA via dietary or supplemental sources. In this review, we examine the role of DHA in optimal cognition during development, adulthood, and aging with a focus on human evidence and putative mechanisms of action.
Omega-3 polyunsaturated fatty acids (PUFAs) exhibit neuroprotective properties and represent a potential treatment for a variety of neurodegenerative and neurological disorders. However, traditionally there has been a lack of discrimination between the different omega-3 PUFAs and effects have been broadly accredited to the series as a whole. Evidence for unique effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and more recently docosapentaenoic acid (DPA) is growing. For example, beneficial effects in mood disorders have more consistently been reported in clinical trials using EPA; whereas, with neurodegenerative conditions such as Alzheimer’s disease, the focus has been on DHA.
DHA is quantitatively the most important omega-3 PUFA in the brain, and consequently the most studied, whereas the availability of high purity DPA preparations has been extremely limited until recently, limiting research into its effects. However, there is now a growing body of evidence indicating both independent and shared effects of EPA, DPA and DHA. The purpose of this review is to highlight how a detailed understanding of these effects is essential to improving understanding of their therapeutic potential. The review begins with an overview of omega-3 PUFA biochemistry and metabolism, with particular focus on the central nervous system, where DHA has unique and indispensable roles in neuronal membranes with levels preserved by multiple mechanisms. This is followed by a review of the different enzyme-derived anti-inflammatory mediators produced from EPA, DPA and DHA. Lastly, the relative protective effects of EPA, DPA and DHA in normal brain aging and the most common neurodegenerative disorders are discussed. With a greater understanding of the individual roles of EPA, DPA and DHA in brain health and repair it is hoped that appropriate dietary recommendations can be established and therapeutic interventions can be more targeted and refined.
n-3 polyunsaturated fatty acids (PUFA) are a subgroup of fatty acids with broad health benefits, such as lowering blood triglycerides and decreasing the risk of some types of cancer. A beneficial effect of n-3 PUFA in diabetes is suggested by some studies. Defective insulin secretion is a fundamental pathophysiological change in both type 1 and 2 diabetes. Emerging studies have provided evidence for a connection between n-3 PUFA and improved insulin secretion from pancreatic β-cells. This review summarizes the recent findings in this regard and discusses the potential mechanisms by which n-3 PUFA influence insulin secretion from pancreatic β-cells.
Unequivocally, genetic variants within the fatty acid desaturase (FADS) cluster are determinants of long chain polyunsaturated fatty acid (LC-PUFA) levels in circulation, cells, and tissues. A recent series of papers have addressed these associations in the context of ancestry; evidence clearly supports that the associations are robust to ethnicity. However, ~80 % of African Americans carry two copies of the alleles associated with increased levels of arachidonic acid compared with only ~45 % of European Americans, raising important questions of whether gene-PUFA interactions induced by a modern western diet are differentially driving the risk of diseases of inflammation in diverse populations, and are these interactions leading to health disparities. We highlight an important aspect thus far missing in the debate regarding dietary recommendations; we contend that current evidence from genetics strongly suggest that an individual’s, or at the very least the population from which an individual is sampled, genetic architecture must be factored into dietary recommendations currently in place.
The problem of mass diabetes is steadily increasing everyday. This editorial introduces key issues that need to be addressed to support the effective control of diabetes in India as well as globally. Issues like awareness generation for risk reduction, frequency of monitoring for selected parameters, standards for monitoring chronic complications in patients with diabetes, and current recommended targets of various parameters, amongst others, are presented along with extensions to the vaccinations recommended for diabetic patients.
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 ∼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, that are being exported to the rest of the world
Omega-3 (ω-3) very long chain polyunsaturated fatty acids (VLC-PUFAs) such as eicosapentaenoic acid (EPA; 20:5 Δ5,8,11,14,17) and docosahexaenoic acid (DHA; 22:6 Δ4,7,10,13,16,19) have been shown to have significant roles in human health. Currently the primary dietary source of these fatty acids are marine fish; however, the increasing demand for fish and fish oil (in particular the expansion of the aquaculture industry) is placing enormous pressure on diminishing marine stocks. Such overfishing and concerns related to pollution in the marine environment have directed research towards the development of a viable alternative sustainable source of VLC-PUFAs. As a result, the last decade has seen many genes encoding the primary VLC-PUFA biosynthetic activities identified and characterized. This has allowed the reconstitution of the VLC-PUFA biosynthetic pathway in oilseed crops, producing transgenic plants engineered to accumulate ω-3 VLC-PUFAs at levels approaching those found in native marine organisms. Moreover, as a result of these engineering activities, knowledge of the fundamental processes surrounding acyl exchange and lipid remodelling has progressed. The application of new technologies, for example lipidomics and next-generation sequencing, is providing a better understanding of seed oil biosynthesis and opportunities for increasing the production of unusual fatty acids. Certainly, it is now possible to modify the composition of plant oils successfully, and, in this review, the most recent developments in this field and the challenges of producing VLC-PUFAs in the seed oil of higher plants will be described.
Caenorhabditis elegans FAT-2 has been characterized as fatty acid Δ12-desaturase able to desaturate C16 and C18 fatty acids. However, in this report we show that when expressed in yeast cells this enzyme can also catalyze Δ15 desaturation. This results in the production of both linoleic acid (ω6 C18:2Δ9,12) and linolenic acid (ω3 C18:3Δ9,12,15) from oleic acid (C18:1Δ9) substrate, and hexadecadienoic acid (ω4 C16:2Δ9,12) and hexadecatrienoic acid (ω1 C16:3Δ9,12,15) from palmitoleic acid (C16:1Δ9) substrate. In addition, this enzyme can also produce C14:2Δ9,12, C15:2Δ9,12, C17:2Δ9,12, and C18:4Δ6,9,12,15 when C14:1Δ9, C15:1Δ9, C17:1Δ9, and C18:3Δ6,9,12 substrates are available in yeast cells. Mass spectrometry analysis of 2,4-dimethyloxazoline modification of fatty acid methyl esters confirms the positions of all newly formed double bonds. These results indicate that when expressed in yeast the C. elegans Δ12-desaturase CeFAT-2 shows a characteristic of a bifunctional Δ12/Δ15-desaturase and has a great deal of elasticity with respect to fatty acid chain length in being able to accept fatty acids ranging from C14 to C18. Interestingly, despite possessing a bifunctional Δ12/Δ15 desaturation activity, phylogenetic analysis suggests that C. elegans Δ12-desaturase CeFAT-2 might have arisen independently from other reported dual Δ12/Δ15-desaturases from fungi and protozoa.
We investigated the relationship between fatty acid desaturase (FADS) gene polymorphisms and insulin resistance (IR) in association with serum phospholipid polyunsaturated fatty acid (FA) composition in healthy Korean men.
Healthy men (n = 576, 30 ~ 79 years old) were genotyped for rs174537 near FADS1 (FEN1-10154G>T), FADS2 (rs174575C>G, rs2727270C>T), and FADS3 (rs1000778C>T) SNPs. Dietary intake, serum phospholipid FA composition and HOMA-IR were measured.
Fasting insulin and HOMA-IR were significantly higher in the rs174575G allele carriers than the CC homozygotes, but lower in the rs2727270T allele carriers than the CC homozygotes. The proportion of linoleic acid (18:2ω-6, LA) was higher in the minor allele carriers of FEN1-10154G>T, rs174575C>G and rs2727270C>T than the major homozygotes, respectively. On the other hand, the proportions of dihomo-γ-linolenic acid (20:3ω-6, DGLA) and arachidonic acid (20:4ω-6, AA) in serum phospholipids were significantly lower in the minor allele carriers of FEN1-10154 G>T carriers and rs2727270C>T than the major homozygotes respectively. AA was also significantly lower in the rs1000778T allele carriers than the CC homozygotes. HOMA-IR positively correlated with LA and DGLA and negatively with AA/DGLA in total subjects. Interestingly, rs174575G allele carriers showed remarkably higher HOMA-IR than the CC homozygotes when subjects had higher proportions of DLGA (≥1.412% in total serum phospholipid FA composition) (P for interaction = 0.009) or of AA (≥4.573%) (P for interaction = 0.047).
HOMA-IR is associated with FADS gene cluster as well as with FA composition in serum phospholipids. Additionally, HOMA-IR may be modulated by the interaction between rs174575C>G and the proportion of DGLA or AA in serum phospholipids.
Background
Dietary fatty acid intake may play a major role in the prevention and management of lifestyle related diseases, like type 2 diabetes mellitus (T2DM). Therefore, the present study aims to find an association between omega 6/omega 3 ratio and type 2 diabetes mellitus.
Methodology
Fasting plasma glucose, glycated hemoglobin (HbA1c) and insulin were measured using commercially available kits. Fatty acid methyl esters were prepared using standard protocols. Delta 5 desaturase (D5D) and delta 6 desaturase (D6D) activities were determined from product-to-precursor ratios of individual fatty acids in plasma. Statistical analysis was performed using SPSS 20.0.
Results and Discussion
Omega 6/omega 3 ratio was higher in the diabetic group (13:1) when compared to that of the non-diabetic group (4:1) and was statistically significant (p<0.0001). Further association studies, showed that univariate model with omega 3/omega 6 ratio and a multivariate model with D5D, D6D, and omega 6/omega 3 ratio could serve as predictive PUFA (polyunsaturated fatty acid) pathway models for T2DM.
Conclusion
From the study results, it is evident that omega 6/omega 3 fatty acid ratios can serve as an essential predictive biomarker in the management of T2DM. This would not only help in management but also in prevention of increased type 2 diabetes incidence in India. Thereby potentiates the need to maintain an ideal balance of omega 6/ omega 3 ratio as prevention is always better than cure.
The study aims to establish the allele and genotype frequency of rs174575 single nucleotide polymorphism in the FADS 2 gene and to find if this variant has any role in the etiology of type 2 diabetes mellitus. The study included two groups- 100 healthy volunteers as the control group and 100 patients with type 2 diabetes as the study group. Fasting blood samples collected, DNA isolated and quantified. The FADS2 gene was genotyped for the allelic polymorphism rs174575, using Sanger sequencing method. In our study, in the control group allele frequency of C is 0.92 (92%) and G is 0.08(8%). Whereas in the study group allele frequency of C is 0.90 (90%) and G is 0.099 (10%). Genotype frequency of CC, CG and GG in the control group is 0.8464 (84.64%), 0.1472(14.72%) and 0.0064(0.64%) respectively. In the study genotype frequency of CC, CG and GC in is (0.807)81.73%, (0.0144)1.44% and (0.177) 16.83% respectively. The results of the study are in accord with the global and livewello stats for rs174575 where the frequency of variant allele G is less when compared to the wild-type allele G. Our study could not find any association of this variant concerning the disease etiology. Further studies with large sample size may exenterate the findings.
EPA and DHA appear to be the most important n -3 fatty acids, but roles for n -3 docosapentaenoic acid are now also emerging. Intakes of EPA and DHA are usually low, typically below those recommended. Increased intakes result in higher concentrations of EPA and DHA in blood lipids, cells and tissues. Increased content of EPA and DHA modifies the structure of cell membranes and the function of membrane proteins. EPA and DHA modulate the production of lipid mediators and through effects on cell signalling can alter the patterns of gene expression. Through these mechanisms, EPA and DHA alter cell and tissue responsiveness in a way that often results in more optimal conditions for growth, development and maintenance of health. DHA has vital roles in brain and eye development and function. EPA and DHA have a wide range of physiological roles, which are linked to certain health or clinical benefits, particularly related to CVD, cancer, inflammation and neurocognitive function. The benefits of EPA and DHA are evident throughout the life course. Future research will include better identification of the determinants of variation of responses to increased intake of EPA and DHA; more in-depth dose–response studies of the effects of EPA and DHA; clearer identification of the specific roles of EPA, docosapentaenoic acid and DHA; testing strategies to enhance delivery of n -3 fatty acids to the bloodstream; and exploration of sustainable alternatives to fish-derived very long-chain n -3 fatty acids.
The AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways and may have therapeutic importance for treating obesity, insulin resistance, type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). Given the ubiquitous expression of AMPK, it has been a challenge to evaluate which tissue types may be most beneficially poised for mediating the positive metabolic effects of AMPK-centered treatments. In this review we evaluate the metabolic phenotypes of transgenic mouse models in which AMPK expression and function have been manipulated, and the impact this has on controlling lipid metabolism, glucose homeostasis, and inflammation. This information may be useful for guiding the development of AMPK-targeted therapeutics to treat chronic metabolic diseases.
White adipose tissue plays an important endocrine role in balancing metabolic homeostasis. During conditions of nutrient excess, as occurs in obesity, there is an expansion of adipose tissue mass associated with a state of “low-grade” inflammation in this tissue. This chronic, unresolved inflammation of adipose tissue is deleterious and leads to many pathological sequelae associated with obesity including insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease. Recently, a novel genus of anti-inflammatory and pro-resolving lipid mediators endogenously generated from membrane phospholipid-derived polyunsaturated fatty acids has been identified during the resolution phase of acute inflammation. These molecules have been termed specialized pro-resolving mediators and act not only as “stop-signals” of inflammatory response but also as facilitators of timely resolution of inflammation. In this review, we provide a comprehensive description of the role of these specialized pro-resolving mediators as endogenous counter-regulators of the persistent inflammatory status present in white adipose tissue of obese individuals. In addition, we discuss the potentiality of these molecules as a novel therapy for the prevention of metabolic co-morbidities associated with obesity.
It is known from the past that the quantity of n-6 in the diet directly affects the conversion of n-3 ALA (a-linolenic acid), found in plant foods, to long-chain n-3 icosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which protect us from disease consumption of omega-6 fats increased at the expense of n-3 fats. This change was due to both the advent of the modern vegetable oil industry and the increased use of cereal grains as food for domestic livestock which in turn altered the fatty acid profile of meat that humans consumed. Study suggests that our ancestors consumed omega-6 and omega-3 fats in a ratio of roughly 1:1. It also indicates that both ancient and modern hunter-gatherers were free of the modern inflammatory diseases, like heart disease, cancer and diabetes, that are the primary causes of death and morbidity today. At the onset of the ind ustrial revolution (about 140 years ago), there was a marked shift in the ratio of n-6 to n-3 fatty acids in the diet. From this, it is concluded that it's all about balance this balance affects things on a cellular level with your omega-3 and omega-6 ratio. Average intake of n-6 fatty acids is between 10 and 25 times higher than evolutionary norms. In this review, the importance of flaxseed and ratio of omega-3 and omega-6 in health balance are discussed.
Abstract: It is known from the past that the quantity of n-6 in the diet directly affects the conversion of n-3 ALA (α-linolenic acid), found in plant foods, to long-chain n-3 icosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which protect us from disease consumption of omega-6 fats increased at the expense of n-3 fats. This change was due to both the advent of the modern vegetable oil industry and the increased use of cereal grains as food for domestic livestock which in turn altered the fatty acid profile of meat that humans consumed. Study suggests that our ancestors consumed omega-6 and omega-3 fats in a ratio of roughly 1:1. It also indicates that both ancient and modern hunter-gatherers were free of the modern inflammatory diseases, like heart disease, cancer and diabetes, that are the primary causes of death and morbidity today. At the onset of the industrial revolution (about 140 years ago), there was a marked shift in the ratio of n-6 to n-3 fatty acids in the diet. From this, it is concluded that it’s all about balance this balance affects things on a cellular level with your omega-3 and omega-6 ratio. Average intake of n-6 fatty acids is between 10 and 25 times higher than evolutionary norms. In this review, the importance of flaxseed and ratio of omega-3 and omega-6 in health balance are discussed.
Background:
The role of n-6 (ω-6) polyunsaturated fatty acids (PUFAs) in type 2 diabetes (T2D) is inconclusive. In addition, little is known about how factors involved in PUFA metabolism, such as zinc, may affect the associations.
Objectives:
We investigated the associations of serum n-6 PUFAs and activities of enzymes involved in PUFA metabolism,Δ5 desaturase (D5D) andΔ6 desaturase (D6D), with T2D risk to determine whether serum zinc concentrations could modify these associations.
Design:
The study included 2189 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 y and free of T2D at baseline in 1984-1989. T2D was assessed by self-administered questionnaires, by fasting and 2-h oral-glucose-tolerance test blood glucose measurement at re-examination rounds 4, 11, and 20 y after baseline, and by record linkage to the hospital discharge registry and the reimbursement register on diabetes medication expenses. Multivariate-adjusted Cox proportional hazards regression models were used to analyze associations.
Results:
During the average follow-up of 19.3 y, 417 men developed T2D. Those with higher estimated D5D activity (extreme-quartile HR: 0.55; 95% CI: 0.41, 0.74;P-trend < 0.001) and higher concentrations of total n-6 PUFAs (HR: 0.54; 95% CI: 0.41, 0.73;P-trend < 0.001), linoleic acid (LA; HR: 0.52; 95% CI: 0.39, 0.70;P-trend < 0.001), and arachidonic acid (AA; HR: 0.62; 95% CI: 0.46, 0.85;P-trend = 0.007) had a lower risk and those with higher concentrations of γ-linolenic acid (GLA; HR: 1.28; 95% CI: 0.98, 1.68;P= 0.021) and dihomo-γ-linolenic acid (DGLA; HR: 1.38; 95% CI: 1.04, 1.84;P-trend = 0.005) and higher D6D activity had a higher (HR: 1.50; 95% CI: 1.14, 1.97;P-trend < 0.001) multivariate-adjusted risk of T2D. Zinc mainly modified the association with GLA on T2D risk, with a higher risk observed among those with serum zinc concentrations above the median (P-interaction = 0.04).
Conclusions:
Higher serum total n-6 PUFA, LA, and AA concentrations and estimated D5D activity were associated with a lower risk of incident T2D, and higher GLA and DGLA concentrations and estimated D6D activity were associated with a higher risk. In addition, a higher serum zinc concentration modified the association of GLA on the risk of T2D.
In the 40 years since the essentiality of polyunsaturated fatty acids (PUFA) in fish was first established by determining quantitative requirements for 18:3n − 3 and 18:2n − 6 in rainbow trout, essential fatty acid (EFA) research has gone through distinct phases. For 20 years the focus was primarily on determining qualitative and quantitative EFA requirements of fish species. Nutritional and biochemical studies showed major differences between fish species based on whether C18 PUFA or long-chain (LC)-PUFA were required to satisfy requirements. In contrast, in the last 20 years, research emphasis shifted to determining “optimal” levels of EFA to support growth of fish fed diets with increased lipid content and where growth expectations were much higher. This required greater knowledge of the roles and functions of EFA in metabolism and physiology, and how these impacted on fish health and disease. Requirement studies were more focused on early life stages, in particular larval marine fish, defining not only levels, but also balances between different EFAs. Finally, a major driver in the last 10–15 years has been the unavoidable replacement of fish oil and fishmeal in feeds and the impacts that this can have on n − 3 LC-PUFA contents of diets and farmed fish, and the human consumer. Thus, dietary n − 3 in fish feeds can be defined by three levels. Firstly, the minimum level required to satisfy EFA requirements and thus prevent nutritional pathologies. This level is relatively small and easy to supply even with today's current high demand for fish oil. The second level is that required to sustain maximum growth and optimum health in fish being fed modern high-energy diets. The balance between different PUFA and LC-PUFA is important and defining them is more challenging, and so ideal levels and balances are still not well understood, particularly in relation to fish health. The third level is currently driving much research; how can we supply sufficient n − 3 LC-PUFA to maintain these nutrients in farmed fish at similar or higher levels than in wild fish? This level far exceeds the biological requirements of the fish itself and to satisfy it we require entirely new sources of n − 3 LC-PUFA. We cannot rely on the finite and limited marine resources that we can sustainably harvest or efficiently recycle. We need to produce n − 3 LC-PUFA de novo and all possible options should be considered.
The Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People was the result of a meeting held at the Rockefeller Foundation Bellagio Center in the fall of 2012. The meeting was science based but policy oriented. The Bellagio Report concluded that: (1) sugar consumption, especially in the form of high-energy fructose in soft drinks, poses a major and insidious health threat, particularly for children; (2) current diets in most populations, albeit with regional differences, are deficient in omega-3 fatty acids but too high in omega-6 fatty acid intake, and (3) not all calories are the same since calories from different sources (i.e. glucose or fructose or omega-6 or omega-3 fatty acids) have different metabolic and neurohormonal effects. This paper summarizes the scientific progress and policy actions that have occurred in these three areas. Genetic variation in populations and gene-nutrient interactions are fundamental concepts that need to be taken into consideration in growth and development and in the prevention and management of chronic noncommunicable diseases since there is enormous variation in both the frequency of genetic variants and dietary composition worldwide. Furthermore, this paper updates the Bellagio Report in terms of the scientific and policy aspects, both of which have expanded over the past 2 years, and describes the progress made in establishing an International Network of Centers for Genetics, Nutrition and Fitness for Health. © 2015 S. Karger AG, Basel.
Type 2 diabetes is a serious and common chronic disease resulting from a complex inheritance-environment interaction along with other risk factors such as obesity and sedentary lifestyle. Type 2 diabetes and its complications constitute a major worldwide public health problem, affecting almost all populations in both developed and developing countries with high rates of diabetes-related morbidity and mortality. The prevalence of type 2 diabetes has been increasing exponentially, and a high prevalence rate has been observed in developing countries and in populations undergoing "westernization" or modernization. Multiple risk factors of diabetes, delayed diagnosis until micro- and macro-vascular complications arise, life-threatening complications, failure of the current therapies, and financial costs for the treatment of this disease, make it necessary to develop new efficient therapy strategies and appropriate prevention measures for the control of type 2 diabetes. Herein, we summarize our current understanding about the epidemiology of type 2 diabetes, the roles of genes, lifestyle and other factors contributing to rapid increase in the incidence of type 2 diabetes. The core aims are to bring forward the new therapy strategies and cost-effective intervention trials of type 2 diabetes.
Diabetes is fast gaining the status of a potential epidemic in India with more than 62 million diabetic individuals currently diagnosed with the disease.1,2 In 2000, India (31.7 million) topped the world with the highest number of people with diabetes mellitus followed by China (20.8 million) with the United States (17.7 million) in second and third place respectively. According to Wild et al.3 the prevalence of diabetes is predicted to double globally from 171 million in 2000 to 366 million in 2030 with a maximum increase in India. It is predicted that by 2030 diabetes mellitus may afflict up to 79.4 million individuals in India, while China (42.3 million) and the United States (30.3 million) will also see significant increases in those affected by the disease.3,4 India currently faces an uncertain future in relation to the potential burden that diabetes may impose upon the country. Many influences affect the prevalence of disease throughout a country, and identification of those factors is necessary to facilitate change when facing health challenges. So what are the factors currently affecting diabetes in India that are making this problem so extreme?
Although omega-3 fatty acids have well documented properties which would reduce the cardiovascular (CV) disease risk, the evidence from randomized controlled trials (RCTs) remains inconclusive. We performed a meta-analysis of the available RCTs for investigating the CV preventive effect of administrating at least 1 gram/day, and for at least 1 year, omega-3 fatty acid supplements to patients with existing CV disease.
RCTs published up to March 2013 were searched from PubMed, EMBASE, and the Cochrane Library. Two of us independently reviewed and selected eligible trials.
Of 360 articles retrieved, 11 randomized, double-blind, placebo controlled trials fulfilling inclusion criteria, overall involving 15,348 patients with a history of CV disease, were considered in the final analyses. No statistically significant association was observed for all-cause mortality (RR, 0.89; 95% CI, 0.78 to 1.02) and stroke (RR, 1.31; 95% CI, 0.90 to 1.90). Conversely, statistically significant protective effects were observed for cardiac death (RR, 0.68; 95% CI, 0.56 to 0.83), sudden death (RR, 0.67; 95% CI, 0.52 to 0.87), and myocardial infarction (RR, 0.75; 95% CI, 0.63 to 0.88).
Overall, our results supply evidence that long-term effect of high dose omega-3 fatty acid supplementation may be beneficial for the onset of cardiac death, sudden death and myocardial infarction among patients with a history of cardiovascular disease.
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are able to partly inhibit a number of aspects of inflammation including leukocyte chemotaxis, adhesion molecule expression and leukocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid, production of inflammatory cytokines, and T cell reactivity. In parallel, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonioc acid and EPA and DHA give rise to anti-inflammatory and inflammation resolving resolvins and protectins. Mechanisms underlying the anti-inflammatory actions of n-3 fatty acids include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor kappa B so reducing expression of inflammatory genes, activation of the anti-inflammatory transcription factor NR1C3 (i.e. peroxisome proliferator activated receptor γ?, and binding to the G protein coupled receptor GPR120. These mechanisms are interlinked. In adult humans, an EPA plus DHA intake greater than 2 g per day seems to be required to elicit anti-inflammatory actions, but few dose finding studies have been performed. Animal models demonstrate benefit from n-3 fatty acids in rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and asthma. Clinical trials of fish oil in patients with RA demonstrate benefit supported by meta-analyses of the data. Clinical trails of fish oil in patients with IBD and asthma are inconsistent with no overall clear evidence of efficacy.
Polyunsaturated fatty acids (PUFAs) are essential components of higher eukaryotes. Single cell oils (SCO) are now widely accepted in the market place and there is a growing awareness of the health benefits of PUFAs, such as γ-linolenic acid (GLA), arachidonic acid (ARA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). ARA and DHA have also been used for fortification of infant formulae in many parts of the world. Fish oils are rich sources of DHA and EPA and a limited number of plant oilseeds are good sources of other PUFAs. Marine protists and dinoflagellates, such as species of Thraustochytrium, Schizochytrium and Crypthecodinium are the rich sources of DHA, whereas microalgae like Phaeodactylum and Monodus are good sources of EPA. Species of lower fungi Mortierella accumulate a high percentage of ARA in the lipid fraction. In this paper, various microbiological and enzymatic methods for synthesis of PUFAs are discussed.
All fats, including saturated fatty acids, have important roles in the body. However, the most important fats are those that the body cannot make and thus must come from the food we eat. These essential fatty acids (EFAs) are based on linoleic acid (omega-6 group) and alpha-linolenic acid (omega-3 group). We need both groups of essential fatty acids to survive. For various reasons EFA deficiency is common in the general population, as is a disproportionate intake of omega-6 fatty acids over omega-3 fatty acids. As such, it is important to eat the right foods to make sure that you're taking in enough and the right kinds of the essential fatty acids. However, there is much more to the story. Studies have shown that increasing the intake of certain essential fatty acids, either alone or in combination with other fats and compounds, can increase health, help in treating certain diseases, and even improve body composition, mental and physical performance.
Exposure to polyunsaturated fatty acids (PUFAs) in early life may influence adiposity development.
We examined the extent to which prenatal n-3 (omega-3) and n-6 (omega-6) PUFA concentrations were associated with childhood adiposity.
In mother-child pairs in the Project Viva cohort, we assessed midpregnancy fatty acid intakes (n = 1120), maternal plasma PUFA concentrations (n = 227), and umbilical cord plasma PUFA concentrations (n = 302). We performed multivariable regression analyses to examine independent associations of n-3 PUFAs, including docosahexaenoic and eicosapentaenoic acids (DHA + EPA), n-6 PUFAs, and the ratio of n-6:n-3 PUFAs, with child adiposity at age 3 y measured by the sum of subscapular and triceps skinfold thicknesses (SS + TR) and risk of obesity (body mass index ≥95th percentile for age and sex).
Mean (±SD) DHA + EPA intake was 0.15 ± 0.14 g DHA + EPA/d, maternal plasma concentration was 1.9 ± 0.6%, and umbilical plasma concentration was 4.6 ± 1.2%. In children, SS + TR was 16.7 ± 4.3 mm, and 9.4% of children were obese. In the adjusted analysis, there was an association between each SD increase in DHA + EPA and lower child SS + TR [-0.31 mm (95% CI: -0.58, -0.04 mm) for maternal diet and -0.91 mm (95% CI: -1.63, -0.20 mm) for cord plasma] and lower odds of obesity [odds ratio (95% CI): 0.68 (0.50, 0.92) for maternal diet and 0.09 (0.02, 0.52) for cord plasma]. Maternal plasma DHA + EPA concentration was not significantly associated with child adiposity. A higher ratio of cord plasma n-6:n-3 PUFAs was associated with higher SS + TR and odds of obesity.
An enhanced maternal-fetal n-3 PUFA status was associated with lower childhood adiposity.