Omega-3 fatty acids: Keys to nutritional health
Abstract
This volume argues for the importance of essential nutrients in our diet. Over the last two decades there has been an explosion of research on the relationship of Omega-3 fatty acids and the importance of antioxidants to human health. Expert authors discuss the importance of a diet rich in Omega-3 Fatty acids for successful human growth and development and for the prevention of disease. Chapters highlight their contribution to the prevention and amelioration of a wide range of conditions such as heart disease, diabetes, arthritis, cancer, obesity, mental health and bone health. An indispensable text designed for nutritionists, dietitians, clinicians and health related professionals, Omega-3 Fatty Acids: Keys to Nutritional Health presents a comprehensive assessment of the current knowledge about the nutritional effects of Omega-3 fatty acids and their delivery in foods. © Springer International Publishing Switzerland 2016. All rights reserved.
Chapters (40)
Supplementation of all essential nutrients in daily diet is must, and omega-3 is the most crucial nutrient today. Anti-nutrients, pollutants should be avoided. Good nutrition helps to renew our body with healthy cells. Seemingly, opposite acting metabolism in both plants and animal life-forms works for creating reducing atmosphere, by deriving NADH and NADPH, reduced molecules, and by processing the food within plant cell and animal cell. Life is a process of defeating entropy, to keep the oxidative stress in check. Vegetarianism is healthier, naturally richer in antioxidants, the reduced molecules. Unlike plant forms, we are crippled in evolution and we need 40 odd essential nutrients to keep our body in a healthy state. Adequate supply of all the essential nutrients, at all times, is pivotal to keep all our faculties fit and fine till last. Although homeostasis keeps metabolites within normal limits, occasional drift by a process called allostasis may also be necessary by a way of readjustment. Redox seems to be playing a very vital role in every cell’s decision, to either remain in a healthy state of life, disease state or die or become immortal and assume a cancerous state.
Today, it is very well established that omega-3 deficiency in modern man’s diet is a major contributing factor for the phenomenal rise in non-communicable diseases, for both its incidences, and severity. Bring back omega-3 fatty acid into food chain has been a global cry. Based on the Danish observation that Eskimos have very low incidences of cardiovascular disease, who eat lot of fish fat rich in omega-3 long-chain fatty acids, fish consumption and fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) became popular as cardioprotective measure. However, a recent study that has shown a specific desaturase mutation to suit their high-fish-fat diet has casted doubt as to whether the same is applicable to rest of the population taking high carbohydrate diet. It has to be appreciated that alpha-linolenic acid (ALA), obtainable from plant source, is the primary essential fatty acid from which EPA and DHA can be derived in our body. ALA is the only form of omega-3 fatty acid available to vegetarians. Flax seed (also called linseed) is the richest vegetarian, sustainable source of omega-3 fatty acid, and fish source is fast dwindling. However, resourcing ALA from linseed had several challenges. We developed a unique innovative concept called “Flax Bio-village” to deal with these challenges. ALA in India linseed is a neglected crop. To increase the area under production, linseed agriculture had to be made lucrative to the farmer by providing high-yielding variety and also good price to lure him to linseed agriculture. Linseed is not readily edible and does contain certain anti-nutrients, and technology is needed to ensure that human food is enriched with omega-3 resourced from linseed devoid of anti-nutrients. ALA is notoriously unstable and becomes rancid very fast. Omega-3 oil had to be cold press extracted under non-oxidizing conditions and stabilized in emulsion to enrich food products. The leftover cake is processed to develop omega-3-enriched feed mixes (EFMs) that when fed to layer and broiler birds can give omega eggs or omega-3 chicken, respectively. Omega-3 emulsion serves as omega-3 fortifier to enrich dairy products including milk. Flax Bio-village Concept (FBC) therefore successfully brings about backward linkage with the farmer and forward linkage with consumer. Concept constitutes finest example of convergence of agriculture to health and wealth. Concept has been validated, but needs huge support and endorsement of industries, public and private sectors to reap the full benefits, and omega-3 nutritional security and “health for all.”
This paper deals with status of linseed research in India which happens to be an ancient oil and fibre-producing crop predominantly cultivated under rainfed condition. Crop systematics in order to establish evolutionary relationship among different sections is very much desired. Cytogenetic studies among the species with different chromosome numbers (2n = 16–80) have revealed that speciation in the genus Linum has taken place in two steps. During the last five decades, spectacular progress has been witnessed in the field of varietal development, and as of now, 65 high seed and oil yielding varieties with resistance to major diseases were released and recommended for general cultivation in different agro-climatic regions of the country. Besides this, improved production and protection technologies have also been developed to harness the production and productivity of the crop. Scope for genetic modifications of fatty acid compositions of linseed oil and oil cake and transfer of novel resistance genes from wild spp. to cultivated ones through biotechnological interventions has also been discussed.
Alpha-linolenic acid (ALA) is important constituent in human breast milk. Omega-3-fatty acid (n-3-FA) plays an important role in infants post birth development; omega-3-fatty acids are obtained from breast milk. Traditionally, cattle grazed in the field and get some omega-3 fatty acid from the green pastures. However, now, they are fed with defined diet solely for getting high milk yield, which resulted in deficiency in omega-3 fatty acid in milk. Various attempts have been made to fortify food products with omega-3 fatty acid. Fortification of food with n-3-FA may offer an effective way of increasing omega-3 long-chain polyunsaturated fatty acid intakes. Recent data indicate that blend of dairy lipids and omega-3-fatty acid from vegetarian oil, can potentiate higher levels of n-3 LC-PUFA levels endogenously. Enriching cattle milk by feeding omega-3-rich cattle feed is also not straight forward. Biofortification is not possible and is met with a biological hurdle in the cattle, as they are ruminants. Several attempts have been made to fortify milk with omega-3 fatty acid or preparation of omega-3-fortified formula milk for infants. Further this chapter reviews crucial role of omega-3-milk in human health especially in mother and child health.
Today, the most prevalent causes of mortality in the developed and developing countries are those associated with cardiovascular diseases (CVD). This fact has raised concern about the relationship between health and diet, in general, and the dietary lipid profile, in particular. The consumer’s awareness about health benefits of omega-3 polyunsaturated fatty acids (n-3 PUFA) is ever increasing. The modern diet is deficient in n-3 PUFA; hence, worldwide efforts, to bring back omega-3 in food chain, are going on. The real task is to make n-3 PUFA a part of their daily wellness strategy. The real challenge is to offer the consumers a wide variety of products which fit into their life style and increase their acceptability. For this purpose, various functional foods fortified with omega-3 are being developed. Among a variety of omega-3-fortified food products, one of the most popular and the innovative functional food is omega-3-enriched egg. As birds are monogastric, the fatty acid composition of bird’s diet usually reflects the fatty acid composition of eggs. Obviously changing the hens’ diet, the fatty acid profile in the eggs can be modified. The inclusion of n-3 PUFA in poultry products is achievable by feeding n-3 PUFA-rich diets to birds. The aim of increasing the n-3 PUFA content of poultry products is to augment the omega-3 consumption in humans. This has opened the possibility to develop “omega-3 eggs” with higher levels of n-3 PUFA for the health-conscious consumer at premium prices. This article reviews the various aspects of omega-3 eggs development, market potential, and health benefits.
Hyperlipidaemia is a multifaceted risk factor for cardiovascular disease, involving multiple aetiologies such as diet, lifestyle, and/or metabolic effects within the body. Dietary long-chain omega-3 polyunsaturated fatty acids (n-3PUFA) have been shown to regulate key pathways involved in lipid metabolism. By this action, n-3PUFA favourably modulate blood lipids such as triglycerides (TG), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). The hypolipidaemic effects of dietary supplementation with n-3PUFA may be enhanced by combination drug or natural therapies and have the potential to reduce dependence on lipid-lowering drug therapy. The widespread modulatory effects on blood lipid profile are not only dose dependent, but also dependent on genetic make-up and gender differences. Further investigation into the modulatory effects of dietary n-3PUFA on blood lipids is warranted in order to optimize the efficacy of n-3PUFA therapy for the prevention and management of hyperlipidaemias. Future studies should investigate the influence of gender and genotypic variants on the effects of dietary n-3PUFA in order to optimize dietary strategies and recommendations to prevent and manage hyperlipidaemias.
Today foods are not intended only to satisfy hunger and to provide necessary nutrients for humans but also to prevent nutrition-related diseases and improve physical and mental well-being of the consumers. The increased knowledge on the relationship between nutrients and health has resulted in several new product categories, such as functional foods and nutraceuticals. A function food is one which demonstrates to affect beneficially one or more target functions in the body, beyond its nutritional effects. Functional foods are concerned with the prevention of disease or reduction of disease risk, but cannot make any claims as to cures. The term nutraceuticals was first introduced by DeFelice in 1989 and in 1994 defined as “any substance that may be considered a food or part of a food which provides medical or health benefits, including the prevention and treatment of disease” (DeFelice in What is a true nutraceutical?—and—What is the nature & size of U.S. nutraceutical market? The Foundation for Innovation in Medicine, Cranford, 1994). Nutraceuticals are functional foods capable of modifying one or more organic functions favorably in addition to their nutritional effect. Probiotics and omega-3 fatty acids are the important nutraceutical ingredients that promise maximum growth over the next five years. Out of various groups of nutraceuticals, the most sought group is the products containing or enriched with omega-3 fatty acids. This article reviews the world market of such products.
Essential fatty acids (EFAs) are key strategic ingredients currently being actively considered for fortification of food by several food and beverage companies to impart known health benefits and value addition, to their food products. Increasing consumer awareness of the health benefits of the essential fatty acids, particularly omega-3s, is generating a wealth of opportunities for their use in functional foods. In recent years, a plethora of omega-3-fortified food products have reached the market, ranging from meat, eggs, and dairy products to cereals, cereal bars, and infant formula. This article reviews various aspects of omega-3 fortification of food products and highlights the compliance of regulatory guidelines applicable to such products.
Marine algae are non-vascular photoautotrophic organisms containing chlorophyll. They are the primary producers in marine food webs, and responsible for the maintenance of life in many ecosystems. Algae are able to produce a wide range of active metabolites, many of which are of great importance to human health, such as the highly valued omega-3 eicosapentaenoic and docosahexaenoic acids (EPA and DHA). There is an increasing demand of these fatty acids, and new sources from algae are been investigated. As presented in this chapter, algae offer great potential and different biotechnological approaches have been developed for boosting fatty acids yields in microalgae. Many industrial exploitation examples exist and more will follow. Thus, in future decades with the scientific advances to come, marine algae will surely become an important, attractive, continuous and sustainable omega-3 source, to thus satisfy the increasing world demand for these compounds
Omega-3 polyunsaturated fatty acids (PUFAs) have therapeutics and health benefits. It plays an important role in maintaining normal physiological functions and protects cardiovascular diseases. To harness their beneficial health effects, daily consumption of omega-3 fatty acid-fortified food has been recommended. Susceptibility of omega-3 fatty acids to oxidation proved major hurdle in the development of PUFA-enriched food. Lipid oxidation decreases shelf life, nutritional value, consumer acceptability, and functionality of fortified food items. In addition, oxidized products of omega-3 fatty acids are believed to pose serious health hazards. Emulsification of omega-3 fatty acids prevents oxidation and off-flavor formation in foods fortified with omega-3 fatty acids. Emulsion can be made by phase titration, phase inversion, homogenization, and sonication methods. Proteins and polysaccharides are employed as emulsifier and forms coating around oil droplet during the process of emulsion formation. Stability to emulsion of omega-3 fatty acids is further improved by using variety of microencapsulation techniques. Emulsion of omega-3 fatty acids prevents lipid oxidation and offers not only increased stability and shelf life but also better bioavailability.
Inflammation is the root cause of a number of degenerative diseases such as rheumatoid arthritis, inflammatory bowel disease, asthma, multiple sclerosis, and atherosclerosis. Although drugs and biologic agents are effective in inhibiting the inflammatory process but their long-term usage encompasses an increased risk for infections and possibility of developing malignancies. Polyunsaturated fatty acids and their metabolites have revealed their crucial role in pathophysiologic processes of inflammation. Altering fatty acid type and their composition in phospholipids of immune cells through diet supplements has proved beneficial in controlling the clinical outcomes in inflammatory diseases. The types of fatty acids being esterified in membrane phospholipids provide a characteristic fatty acid composition of the phospholipids which can dictate the characteristics of the inflammatory response depending on the types of metabolites of polyunsaturated fatty acids formed through the lipoxygenase and cyclooxygenase pathways, either promoting or inhibiting the inflammatory process, by controlling intracellular signaling pathways. Therefore, dietary management through supplementation of omega-3 fatty acids is sought as an alternative approach for clinical management of inflammatory diseases.
Worldwide, the incidences of cancer are rising. Various environmental and genetic factors are predisposing individuals to cancer. Majority of these factors result in upregulation of pro-survival pathways, downregulation of tumor suppressors, and chronic inflammation. The ratio of w-6/w-3 polyunsaturated fatty acids (PUFAs) plays very crucial role in the initiation and progression of cancer. Low w-6/w-3 PUFA ratio has been shown beneficial in managing the hallmarks of cancer cell. Enormous data from cancer cell line and in vivo cancer models have given insight into the mechanisms underlying the anticancer effects of w-3 PUFAs. Here, we discussed major possible mechanisms for beneficial effects of w-3 PUFAs as evidenced by the preclinical in vitro cancer cell line models and in vivo models.
Linseed has been cultivated for at least 8000 years and is now a major oilseed crop in many countries. The major components with potential therapeutic uses are the essential n-3 fatty acid, α-linolenic acid (ALA), lignans such as secoisolariciresinol diglucoside (SDG) and carbohydrates such as mucilages containing arabinoxylans. ALA is orally bioavailable and may be stored or converted into longer chain n-3 fatty acids such as eicosapentanenoic acid (EPA) and docosahexaenoic acid (DHA) and other bioactive lipid metabolites. In most studies in humans, whole linseed improves insulin sensitivity, linseed flour but not oil attenuates the pro-inflammatory state and linseed oil but not the lignan fraction benefits osteoporotic bone in obese or overweight patients. SDG is metabolised in the intestine to the mammalian lignans, enterodiol and enterolactone. Treatment with SDG may improve metabolic parameters, decrease the progression of atherosclerosis and protect the heart, liver and kidneys but does not seem to decrease obesity or blood pressure. The fibre present in linseeds may improve gastrointestinal function. Thus, there is considerable evidence that the constituents of linseed, especially ALA and probably SDG and fibre to a lesser extent, either separately or combined, can be defined as a functional food as they improve the multi-organ changes induced by obesity. However, the patient groups that will benefit most still need to be defined, and this may also be helped by clearer definition of the molecular mechanisms.
Obesity leads to several chronic morbidities including type 2 diabetes, dyslipidemia, atherosclerosis, and hypertension, which are major components of the metabolic syndrome (MetS). Low-grade inflammation has been identified as a key factor in the development of MetS features affecting obese subjects. Several studies have proposed beneficial effects of the omega-3 polyunsaturated fatty acids (n-3 PUFAs) for the prevention and amelioration of MetS features. In this chapter, we will focus on reviewing randomized, controlled trials that evaluate the effects of supplementation with marine-derived EPA and DHA on weight loss, insulin sensitivity, lipid metabolism, blood pressure, and inflammation in overweight/obese subjects with MetS characteristics. Supplementation with n-3 PUFAs may be an interesting therapy to reduce hypertriglyceridemia and hypertension, while the ability of n-3 PUFAs to promote weight loss, insulin sensitivity, and changes in cholesterol metabolism in patients with MetS remains controversial. The role of n-3 PUFAs-derived proresolving lipid mediators such as resolvins, protectins, and maresins in MetS is also discussed.
Fats and oils are the essential constituents of human diet, and nearly 80 % of these are obtained from plants. The predominant fatty acids present in plant oils are saturated and unsaturated compounds with straight aliphatic chains of carbon atoms and a single carboxyl group. Depending on the position of the first double bond from the methyl (ω) end in the fatty acyl chain, the mono- and polyunsaturated fatty acids can be denoted as ω-9, ω-6, or ω-3. Excess consumption of ω-6 fatty acids has greatly and unfavorably increased the ω-6: ω-3 ratio up to 25:1, which is associated with prevalence of many negative health effects, including cardiovascular diseases, cancer, osteoporosis, and inflammatory and autoimmune diseases. Because the ω-3 fatty acids (FAs) are the precursors for synthesis of anti-inflammatory eicosanoids, balancing the ω-6: ω-3 ratio is vital. The easiest approach to achieve this would be consumption of oils rich in ω-3 FAs, such as linseed oil. Alternatively, the fatty acid biosynthetic pathway in plants producing high ω-6 FAs can be altered by biotechnological means, so that they produce higher proportion of ω-3 FAs. This chapter describes the current knowledge of the fatty acid biosynthesis pathway in plants, including the genes involved, their temporal and spatial expression patterns, and various fluxes that they drive. The choice of oilseeds, genes, and promoters for modulating the fatty acid biosynthesis flux from ω-6 to ω-3 fatty acids is also dealt with. The potential hurdles in achieving these and possible solutions have also been described.
All forms of diabetes are characterized by hyperglycemia and macro- and micro-angiopathy which in turn lead to several complications viz. nephropathy, cardiomyopathy, retinopathy, neuropathy, and loss of RBC deformability. Also, the fatty acid elongase and desaturase activities are known to decrease in diabetes. The present review tries to summarize the link between omega-3 fatty acids and diabetic complications. Thus, reports in the literature suggest that supplementation with omega-3 fatty acid, especially eicosapentaenoic acid (EPA, 20:5, n-3), showed beneficial effect in diabetic nephropathy by improving the renal function in human as well as in the experimental animal studies. DHA plays a major role in signaling cascades and rhodopsin regeneration, while insufficiency of DHA is associated with impairment of retinal function; supplementation with DHA improved the retinal function. While omega-3 polyunsaturated fatty acids (PUFAs) offered protection against cardiovascular diseases, omega-6 PUFAs also showed cardioprotective action. Supplementation with omega-3 fatty acids improved nerve conduction velocity (NCV) and Na+, K+-ATPase activity in diabetic neuropathy. Omega-3 fatty acids increased red blood cell (RBC) deformability and decreased plasma viscosity, thereby helping in improving cardiomyopathy associated with RBC deformability.
Mitochondrial disease (MD) generally refers to a group of disorders that are attributable to malfunctioning mitochondria that are unable to efficiently or effectively generate energy. Some of the most profound effects of MD are seen in the brain and the muscles, while other commonly affected organs include heart, liver, nervous system, eyes, ears, and kidneys. One of the promising nutritional components which may play crucial role in the management of MD is omega-3 polyunsaturated fatty acids (n-3 PUFAs). Animal studies concluded that the omega-3 PUFAs, i.e., ALA and especially EPA and DHA, have some positive effects on functional parameters of mitochondria in various mitochondrial dysfunction-related pathological conditions such as neurodegenerative diseases: Parkinson’s disease, Alzheimer’s disease, aging, cardiovascular diseases, diabetes, and ROS-induced damages. Supplementation with n-3 PUFAs from fish oil (FO) has shown mitochondrial neuroprotective effect in animal models of Parkinson’s disease and aging while clinical trials with patients have shown equivocal results. n-3 PUFAs protected cardiac mitochondria from Ca2+-induced swelling in isoproterenol-treated rats. In animal studies, DHA supplementation brought about significant changes in mitochondria membrane phospholipid components. Similar pattern was noted in cardiac mitochondria from diabetic animal model.
DHA is shown to influence the brain development through the effects on gene expression, monoaminergic neurotransmission or protection against apoptotic cell death. Thus, DHA enhanced neurite outgrowth of hippocampus and cortical neurons and clonal pheochromocytoma (PC12). In experimental animals, diets deficient in omega-3 PUFA resulted in decreased cell size of neurons in hippocampus, hypothalamus and parietal cortex and substantial disturbances in neural function. In aged mice, supplementation with high DHA significantly lowered β-amyloid content by around 70 % with a decrease in the levels of β-amyloid protein 42 (βAP42). Dietary supplementation with DHA partly protected from overexpression of NMDA receptor subunits but fully prevented CaMKII decrease in transgenic mice. The DHA levels were found to be low in the serum and in the brains of AD patients and the levels of total and phosphorylated Tau protein in CSF were high; supplementation with DHA decreased these levels suggesting neuroprotective action. In conclusion, supplementation with DHA may be safe for prophylactic, if not therapeutic application in AD.
Oxidative stress and inflammation are the major mechanisms that contribute to the pathogenesis of neurotraumatic, neurodegenerative, and neuropsychiatric diseases. Two major families of essential fatty acids (omega-6 family and omega-3 family) are known to occur in the mammalian brain. Enzymic and nonenzymic mediators of omega-6 family promote and support oxidative stress and neuroinflammation, whereas enzymic lipid mediators of omega-3 fatty acids retard oxidative stress and inhibit neuroinflammation. Present day Western diet is enriched in omega-6 fatty acids. It contains 15–20 times higher omega-6 fatty acids compared to omega-3 fatty acids. Due to the consumption of Western diet, our bodies are flooded with enzymic (eicosanoids and platelet-activating factor) and nonenzymic (4-hydroxynonenal, malondialdehyde, acrolein, isoprostane, isofuran, and isoketal) lipid mediators of omega-6 fatty acids metabolism leading to oxidative stress and neuroinflammation. Increased consumption of omega-3 fatty acids may result in retardation of oxidative stress and neuroinflammation due to the production of resolvins, neuroprotectins, and maresins. Thus, high levels of omega-3 fatty acids are needed in our diet for the optimal health.
Omega-3 polyunsaturated fatty acids are essential nutrients for healthy individuals. Their beneficial effects in coronary and autoimmune diseases, as well as in diabetes, have been proven numerous times in the past. In addition, their role in maintaining normal physiology of the eyes has been extensively discussed over the last few years, with more emphasis given on their anti-inflammatory effects. From a literature review and some of our observational studies, there is strong evidence to support that supplementation of individuals with omega-3 formulations could lead to disease regression in some types of retinopathies, including age-related macular degeneration and macular dystrophies and also some severe forms of dry eyes. Therefore, using the right dosage regime and with the appropriate supervision, omega-3 supplementation could be a potential therapeutic for different types of oculopathies.
Algal source of omega-3s is good for supplementation of DHA and DPA that mediate to sustain our vascular health. The ratio of DHA and DPA between breast milk and micro algae is comparable and found safe. Hence, supplementation as a component of food is now being accepted at all levels. That option has proven safe for vegetarians, type 2 diabetics, the elderly, and those with fish allergies. DHA is also recommended for pregnant and nursing mothers as a supplement, especially during the 3rd trimester and when nursing. Imperatively, the omega-3 bond can be a powerful co-therapy.
The pathogenesis of postpartum depression remains to be fully elucidated but likely results from the interactions of genetic factors, environmental influences, and the physiological demands of pregnancy, childbirth, and lactation. Epidemiological evidence and clinical findings suggest that low dietary and/or tissue levels of n-3 (omega-3) polyunsaturated fatty acids (PUFA) may be a factor contributing to the etiologies of both major depression and postpartum depression. Animal studies indicate that reproducing females are at particular risk of losing the n-3 PUFA DHA from tissues including the brain. A decrease in brain DHA content causes a number of neurobiological effects that also occur in major depression disorder. This evidence, which supports the involvement of decreased brain n-3 PUFAs in the etiology of postpartum depression and other depressive disorders, and their implications for the prevention and treatment of these disorders, are discussed.
Bone is a metabolically active tissue that undergoes continuous remodeling to cope with the body’s Ca and P requirements and to repair microscopic damage in a dynamic process where osteoblasts are responsible for bone formation and osteoclasts for its resorption. Dietary fat has a clear influence on bone health. Long-chain polyunsaturated fatty acids (LC-PUFAs), especially the omega-3 (ω-3) fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for bone metabolism. Several studies have reported that LC-PUFAs can increase bone formation, affecting peak bone mass in adolescents and reducing bone loss, because LC-PUFAs reduce inflammatory cytokines, increases calcium absorption, and enhances skeletal calcium levels. This chapter summarizes the role of LC-PUFA, especially the ω-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid, on bone health and turnover.
Fe is an essential micronutrient, required for many biological processes. Apart from its role in hemoglobin, it is central to many redox processes throughout the body. The long-chain polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA; 22:6 n−3) is ubiquitously present in the plasma membrane of biological cells and has a key role as an essential macronutrient in all mammals since it participates in a number of biological functions in the maintenance of homeostasis. This chapter summarizes the interactive role of Fe and DHA in physiological situations and nutritional deficiencies and reveals that DHA stimulates Fe metabolism, and several studies have suggested that Fe deficiency is associated with an alteration in tissue fatty acid content and hypomyelination indicating a clear interaction between Fe and DHA metabolism.
Intake of long-chain omega-3 polyunsaturated fatty acids (omega-3 PUFAs) derived from marine sources, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been long recommended by health authorities to provide cardiovascular protection. As a cardiovascular protective agent, omega-3 PUFAs are known to function as natural HMG-CoA reductase and ACE enzyme inhibitors, antiarrhythmic, antihypertensive, anti-atherosclerotic, anti-inflammatory, cyto-protective, and cardio-protective molecules. However, omega-3 PUFAs play different roles on major cardiovascular events according to the diverse patient populations. Although appearing to be a low-risk and cost-effective strategy to improve cardiac health, available evidence demonstrates that omega-3 PUFAs supplementation may be recommended in primary prevention of major cardiovascular events in patients free of known coronary heart disease (CHD), but with high risk. Furthermore, patients with established coronary artery disease (CAD) and previous myocardial infarction (MI) may potentially benefit on causes of mortality from omega-3 PUFAs. However, omega-3 PUFAs may not be effective in preventing major cardiovascular events in patients with peripheral arterial disease (PAD), cardiac arrhythmias, and impaired glucose metabolism. The exact effects of omega-3 PUFAs in some of the various classified cardiovascular conditions may be beneficial and worth exploring.
During the last 3-4 decades, there has been vast information on effect of omega-3 on the immune system in health and in diseases, especially those caused by excessive inflammatory response. In this chapter, attempts have been made to elucidate the effect of omega-3 on different components of immune system, especially during child development and in aged individuals. Omega-3 is also known to reduce the pathological manifestations especially in diseases related to inflammation, allergy and autoimmunity which are the major challenges today. Earlier studies on effect of polyunsaturated fatty acids in immune system were conducted using animal systems; in this chapter, more emphasis is given on human studies. n-3 PUFAs have been shown to be very effective in controlling inflammation by affecting extravasation, phagocytic response, generation of cytokines, inflammatory mediators and adhesion molecules. They also manipulate the functions of antigen-presenting cells and lymphocytes including T and B cells, NK cells, LAK cells and also T regulatory cells. Most of the reports on effect of dietary omega-3 in human health have been conducted as clinical trials, extrapolated from experiences in animals and also using in vitro techniques, which have limitations. The chapter reports trials conducted to assess the effectiveness of omega-3 diet supplementation in healthy volunteers using in vitro and in vivo assays. It also deals with the effect of omega-3 diet supplementation on pregnancy and lactation, especially in relation to infant allergies. Cognizance has also been taken of the effects of omega-3 diet supplementation in aged population. Finally, the chapter reviews important literature on the effectiveness of n-3 PUFAs in controlling inflammatory and autoimmune diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease (IBD), psoriasis, cardiovascular disease, diabetes, multiple sclerosis and systemic lupus erythematosus (SLE).
![Figure 1: 7.1 ‘The absorption spectrum for the DNA molecule’. The graph powerfully makes the generalised point that DNA is potentially very susceptible to UVC in the range 200–290 nm and to a much lesser extent to UVB 290–320 nm. This arguably had significant evolutionary implications imposing faster evolutionary change prior to oxygenation and more stable conditions post-oxygenation, hence scope for more sophisticated life forms. This graph is from ‘Biological Sensors for Solar Ultraviolet Radiation’ by Yagura et al. [28]. I am very grateful and thank them for their kind permission](https://www.researchgate.net/profile/Robert-Brown-82/publication/308188164/figure/fig5/AS:408108900864001@1474312152119/The-absorption-spectrum-for-the-DNA-molecule-The-graph-powerfully-makes-the_Q320.jpg)
![Figure 2: 7.2 Water is partially transparent to UV and visible light; the absorbance varies tremendously depending on the particular content of the water, thus providing a wide selection of possible UV exposures. (The diagram is indicative and drawn from a variety of sources, including ‘UV penetration in the water column’ by Vantrepotte and Mélin [36].) I am very grateful and thank them for their kind permission.)](https://www.researchgate.net/profile/Robert-Brown-82/publication/308188164/figure/fig8/AS:408108900864004@1474312152431/Water-is-partially-transparent-to-UV-and-visible-light-the-absorbance-varies_Q320.jpg)
![Figure 3: 7.3 In an anoxic thermocline water strata layer, of Knaack Lake during a 24-h summer period, water sulphide concentrations were mainly related to the activity of sulphur bacteria and were increased at night from stored sulphate or resupply from below. (The graph is from: ‘The role of phototrophic bacteria in the sulphur cycle of a meromictic lake’ by Parkin and Brock [43].) I am very grateful and thank them for their kind permission.)](https://www.researchgate.net/profile/Robert-Brown-82/publication/308188164/figure/fig7/AS:408108900864003@1474312152355/In-an-anoxic-thermocline-water-strata-layer-of-Knaack-Lake-during-a-24-h-summer-period_Q320.jpg)
Photons energise electrons, fuelling redox reactions. Substrate availability; quantum properties and so potential interactions; environmental conditions, including polarised UV light, volcanic mineral enriched vapour and waters, sulphur, halogen interaction with organocompounds, and zeolites; likely determined the feasibility and evolutionary emergence pathways of chiral biological systems, hence ultimately life and determined the conditions of our existence. Linoleic (LA) and alpha-linolenic (ALA) acids facilitate membrane and vesicle formation; they absorb and are oxidised by ultraviolet light, creating opportunities for signalling, light sensing and energy production. Functional cellular pathways are variously conserved from lower to higher life forms. Plants flourish without AA, EPA and DHA, using LA and ALA for; membrane structure, energy production and storage, immune and defence function, signalling, reproduction and crucially photosynthesis the powerhouse of our terrestrial existence. LA and ALA are preferred substrates of peroxisomes and primary beta-oxidation substrates in plants; they also have fundamental underappreciated metabolic roles in humans including in beta-oxidation. ALA and LA are preferred substrates of LOX enzymes. LOX products, 9 and 13 HODE, are crucial to plant physiology and also the most common plasma oxylipins in humans mainly present in LDL. LA is a key cardiolipin component in plants and humans and key substrate for mitochondrial 4HNE and 13HODE production, affecting apoptosis and ATP regulation. Downstream LA products including 4HNE and MDA have important roles in plants; in humans, they factor in most ‘Western’ non-communicable diseases, including cardiovascular, lung, liver, cancer and neurological conditions. Widespread Western dietary LA excess and ALA deficit have underappreciated functional and so health consequences.
![Figure 3: 8.3 ‘Relative median changes in the plasma concentrations of oxidised LDL (left) and lipoprotein(a) (right) of all the study subjects (n = 37) from baseline to low-fat, low-vegetable diet and from baseline to the low-fat, high-vegetable diet’. From ‘Changes in Dietary Fat Intake Alter Plasma Levels of Oxidised Low-Density Lipoprotein and Lipoprotein(a)’ with very grateful thanks to the authors for permission: Silaste et al. [50]](https://www.researchgate.net/profile/Robert-Brown-82/publication/308190358/figure/fig2/AS:408112600240129@1474313034195/Relative-median-changes-in-the-plasma-concentrations-of-oxidised-LDL-left-and_Q320.jpg)
![Figure 4: 8.4 Reducing dietary LA significantly reduced plasma LA and HODE oxylipins. The data were abstracted from Table 2 of ‘Lowering dietary linoleic acid reduces bioactive oxidised linoleic acid metabolites in humans’ with very grateful thanks to the authors: Ramsden et al. [51]](https://www.researchgate.net/profile/Robert-Brown-82/publication/308190358/figure/fig7/AS:408112600240140@1474313034756/Reducing-dietary-LA-significantly-reduced-plasma-LA-and-HODE-oxylipins-The-data-were_Q320.jpg)
![Figure 5: 8.5 ‘Reducing dietary LA to 1 en% prevents adipose tissue accumulation and reverses the obesogenic effects of a high-fat (60 en%) diet. Animals fed 8 en% LA accumulated more fat than animals fed 1 en% LA. The addition of 1 en% n-3 EPA/DHA to 8 en% LA diets prevented the increase in adipose tissue seen in animals fed 8 % energy LA. The obesogenic properties of a high-fat diet (60 en% fat) were reversed by selective reduction of LA from 8 en% to 1 en% and replacement by greater saturated fat. The animals shown are representative for the animals in each dietary treatment. Upper row; isocaloric medium-fat diets of 35 en% fat, lower row; isocaloric high-fat diets of 60 en% fat. The fatty acid composition, not total fat calories, determined the obesogenic properties of the diets. DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; LA, linoleic acid’. From ‘dietary linoleic acid elevates endogenous 2-AG and anandamide and induces obesity’ with very grateful thanks for permission to the authors: Alvheim et al. [52]](https://www.researchgate.net/profile/Robert-Brown-82/publication/308190358/figure/fig1/AS:408112600240128@1474313034103/Reducing-dietary-LA-to-1-en-prevents-adipose-tissue-accumulation-and-reverses-the_Q320.jpg)
![Figure 6: 8.6 This graph of the predominant oxylipins in plasma is illustrative of the dominance of LA oxylipins over the oxidised products of AA, EPA and DHA, including the COX2 AA prostaglandins. The list only selects the major oxylipins recorded. The figures for PGE2 and PGJ2 have been included to give an indication of comparative concentrations; they were not in the predominant group. The differences between the groups are interesting and particularly the significant disparities of levels of omega-3 oxylipins. The 9,10 DiHOME level is high in comparison with other groups. DiHOMEs may inhibit mitochondrial respiration and increase vascular permeability. Comparison is difficult because ratios of oxylipins differ significantly between groups, as can be seen by comparing these data to the Schuchardt et al. [55], Ramsden data [51] and Spath [22] data, but the general trend that LA oxylipins are the largest group of oxidised lipids in plasma is clear. Omega-3 supplementation by Schuchardt [91] (1008 mg EPA + 672 mg DHA) significantly increased EPA oxylipins compared to baseline, peaking at about 6 h and remaining a little above baseline at 48 h. The graphed data are selectively abstracted from Tables 7, 8 and 9 of the ‘The Human Serum Metabolome’ paper with very grateful thanks to the authors: Psychogios et al. [93]](https://www.researchgate.net/profile/Robert-Brown-82/publication/308190358/figure/fig6/AS:408112600240137@1474313034599/This-graph-of-the-predominant-oxylipins-in-plasma-is-illustrative-of-the-dominance-of-LA_Q320.jpg)
![Figure 8: 8.8 ‘It has been reported in numerous studies that the extent of lipid oxidation is elevated in diseased patients compared to normal subjects’; ‘linoleates are the most abundant PUFAs in vivo’, ‘these products exert cytotoxic and genotoxic effects’; these observations of the authors are supported by figures showing relative levels of hydroperoxyoctadienoic acid (HODEs) in plasma and erythrocytes of patients suffering from a range of common ‘Western diseases’ compared to healthy controls, graphed from selective data abstracted from of ‘Lipid peroxidation biomarkers for evaluating oxidative stress and assessing antioxidant capacity in vivo’. with very grateful thanks to the authors: Yoshida et al. [139]](https://www.researchgate.net/profile/Robert-Brown-82/publication/308190358/figure/fig8/AS:408112600240141@1474313034846/It-has-been-reported-in-numerous-studies-that-the-extent-of-lipid-oxidation-is-elevated_Q320.jpg)
The physiological and metabolic importance of linoleic acid (LA) and alpha linolenic acid (ALA), the LA/ALA balance, their relevance to oxidative stress signalling and metabolic function are underappreciated. LA and ALA followed by other 18-carbon fats are the preferred peroxisomal beta-oxidation substrates. Peroxisomal beta-oxidation products include short-chain fats, ACoA and peroxide. Human function, particularly existence, is conditional on essential nutrients. LA and ALA are the primary lipids in plant material and most common terrestrial lipids; supply is dependent on environmental fecundity; their oxidised products are multiple and bioactive in many pathways, required for reproduction and may ultimately synchronise reproduction to environmental LA availability, control human capacity to reproduce and related mating behavioural characteristics. Oxidised and elongated LA products—key regulators in important biological mechanisms and systems including; macrophage- and microglia-related tissue destruction; creation and repair; oxidative stress-based signalling for; inflammation; immune function and defence; hormone production; pheromones; placental and foetal development; parturition; energy regulation; and fat deposition,—and ultimately control reproductive capacity. This explains why LA oxylipins and related products play central roles in ‘Western’ ‘inflammatory’ non-communicable diseases, including obesity. Oxidised LA products 9 and 13HODEs and family, the most common plasma oxylipins, with parent LA, are important LDL components, and when present in excess with their downstream products including Oxo-HODE, 4HNE and MDA, predicate non-communicable ‘Western’ diseases, with roles in inflammation, tissue repair, maintenance of epithelial cells, macrophage and microglial function. 13HODE is the primary endogenous activator of PPAR gamma; excess PPAR gamma activation, along with iNOS stimulation and NO blocking of peroxisomal catalase production, promotes peroxide-based oxidative stress, including peroxisome-assisted macrophage oxidative burst capacity. Oxidation by peroxide forms highly damaging hydroxyl radicals; down-stream products include 4HNE, which results in increased oxidative stress, thereby activating COX and LOX enzymes. LA and ALA are overall preferred LOX substrates and secondary COX substrates; products include 13HODE. 13HODE via PPAR gamma activates OLR1 and CD36; oxidised LDL receptor activity is associated with ‘Western diseases’ including cancer, diabetes, asthma and neurological, vascular, cardiac, obesity and fertility-related conditions. Intriguingly, OLR1 is ‘oncogenic’. PPAR gamma-related peroxisomes direct ACoA to repair pathways, including cholesterol and fat production via HMGCoA pathways. Energy deficit activates PPAR alpha peroxisomal beta-oxidation pathways. In contrast to PPAR gamma, PPAR alpha and delta activation signals for increased catalase antioxidant production, as well as for production of short-chain fats and ACoA, which is utilised via acetate, malate and ketones production providing alternate substrate for mitochondrial energy production. ALA deficits and excess dietary LA, including from vegetable oil, in the context of ‘Western’ nutrient-depleted pre-oxidised diets are significant health risk factors, including in high-fat low-carbohydrate ‘paleo’ diets. Phosphatidylcholine including of dietary origin is the main component in VLDL, LDL and chylomicron shells; its preference for polyunsaturated fats at the SN2 position gives phosphatidylcholine particular relevance to the delivery of polyunsaturated fats to cells, hence membrane composition and consequent function; for example, LA—a key cardiolipin component—when oxidised in situ reduces mitochondrial function, including ATP metabolism, and ultimately regulates apoptosis. Dietary pre-oxidation increases crosslinking and AGE formation, damaging antioxidant related nutrients including glutathione, related amino acid cysteine, and phyto-antioxidants including fat-soluble vitamin E and retinoids. Pre-oxidised nutrient-depleted diets containing excess LA and deficient in ALA underlie cellular and energy pathway dysfunction, fuelling non-communicable ‘Western diseases’.
![Figure 2: 9.2 Changes in the ALA content of LDL, HDL and plasma, in humans on an isocaloric diet, fed ALA in the form of linseed oil for 2 weeks each at 4–16 % of energy intake. The competitive effects of rising ALA, presumably primarily for the COX enzymes, on AA so the production of prostaglandins PGE2 and PGF2 is thought provoking. The data are abstracted from Tables 2, 3 and 6 of: ‘Effect of alpha-linolenic acid in the human diet on linoleic acid metabolism and prostaglandin biosynthesis’ with very grateful thanks to the authors: Adam et al. [17]](https://www.researchgate.net/profile/Robert-Brown-82/publication/308191430/figure/fig9/AS:408220389658628@1474338733865/Changes-in-the-ALA-content-of-LDL-HDL-and-plasma-in-humans-on-an-isocaloric-diet-fed_Q320.jpg)
![Figure 3: 9.3 The percentage lipid composition of plasma cholesterol esters can be changed significantly by the percentage in calories of OA and LA in dietary fats. The uptake of LA in plasma cholesterol esters shows a tendency to flatten off at higher intakes. The data are abstracted from Table 4, p. 71 of ‘Atherogenic Effect of Different Cholesteryl Esters’ with very grateful thanks to the authors: Gottenbos et al. [59]](https://www.researchgate.net/profile/Robert-Brown-82/publication/308191430/figure/fig8/AS:408220389658627@1474338733791/The-percentage-lipid-composition-of-plasma-cholesterol-esters-can-be-changed_Q320.jpg)
![Figure 4: 9.4 Omega 6 levels in the liver in rats remain relatively high even on very low omega 6 intakes as a percentage of calories, the saturation effect referred to by Professor Lands [64]. LA liver lipid content rises much faster than ALA content. The data are abstracted from Table 2 of ‘The effect of dose level of essential fatty acids upon fatty acid composition of the rat liver’ with very grateful thanks to the authors: Mohrhauer et al. [58]](https://www.researchgate.net/profile/Robert-Brown-82/publication/308191430/figure/fig11/AS:408327017254915@1474364155621/Omega-6-levels-in-the-liver-in-rats-remain-relatively-high-even-on-very-low-omega-6_Q320.jpg)
![Figure 7: 9.7 Lipids in placque based on data abstracted from Table 1 ‘Lipids of human astherosclerotic placques and xanthomas; clues to the mechanism of plaque progression’ with very grateful thanks to the authors; Rapp et al. J. Lipid Res. 1983. 24:1329–1335 [121]](https://www.researchgate.net/profile/Robert-Brown-82/publication/308191430/figure/fig5/AS:408220389658624@1474338733430/Lipids-in-placque-based-on-data-abstracted-from-Table-1-Lipids-of-human-astherosclerotic_Q320.jpg)
The heart, an organ with high ATP requirements, derives 70 % of its energy from fats, primarily delivered by LDL in the fasted state and chylomicrons in the fed state. The primary ‘cause’ of cardiovascular disease is not pure dietary ‘saturated’ fats per se, although excessively oxidised linoleic acid (LA)-rich non-ruminant animal so-called ‘saturated’ fats may well be significant factors, but is arguably due to a mixture of: excess Omega 6 LA intake within the context of a nutrient including antioxidant depleted pre-oxidised western diet, raised plasma oxidative stress including of LDL, damage to cardiolipin species and consequent release of LA oxylipins including 9- and 13-HODE 4-HNE and MDA so increased oxidised stress, consequential and wider oxidative stress related damage to mitochondria including their DNA, hence reduction in cardiac mitochondrial energy output; excess LA oxylipins of dietary and endogenous origin leading to consequent overactivation of oxidised LDL receptors and PPAR gamma pathways, so excess inflammation and immune activation including of iNOS hence raised peroxisomal peroxide-related oxidative stress; PPAR gamma activation by LA HODEs including 9 and 13 HODE and resultant PPAR gamma-related shunting of peroxisomal beta-oxidation product ACoA to lipid and cholesterol production and deposition rather than mitochondrial energy substrate production; and lack of PPAR alpha activation through exercise, fasting, or to a lesser extent by omega 3s, of mitochondrial energy substrate production-related pathways, combined with consequent damage to cell tissue as well as mitochondria, so energy inhibition and resultant malfunction including; inflammation, tissue destruction, and macrophage foam cell related and wider intra and inter-cellular lipid deposition; all facilitated by pre-oxidised excessively refined nutrient and antioxidant depleted, AGE and cross-linked protein, oxidised lipid product-rich, LA ALA-imbalanced, ‘Western’ diets, combined with constant food accessibility, exacerbated by lack of intermeal ‘fasting’ and energy expenditure including exercise.
Current metabolic considerations of “fuel” sources for brain energy, and substrate creation, generally focus on glucose and externally derived ketones. However, the healthy existence of Inuit, with a common Inuit CPT1A carnitine polymorphism that substantially inhibits mitochondrial uptake of long fats, who apparently were not in ketosis, with little access to glucose, suggests humans can fuel their brains largely from peroxisomally produced medium-chain fats (MCFs), ACoA and derivatives. The health, and ability to build and run a brain, of neonates nourished with breast milk, which is high in lipids and low in carbohydrates, whom are very rarely in significant measured ketosis, adds to evidence the brain can metabolise fats as a major energy source. Whilst brain lipid research primarily focuses on arachidonic (AA) and docosahexaenoic acids (DHA); alpha-linolenic (ALA) and linolenic acids (LA), as preferred peroxisomal beta-oxidation substrates, and to lesser extents palmitic (PA) and oleic acids (OA), likely have underappreciated but fundamental roles in the brain as the primary substrates for peroxisomal beta-oxidation, so indirect sources of MCFs, ACoA and downstream-derivatives, mitochondrial “fuels” for ATP production. Alternatively ACoA is a substrate for “endogenous” lipid manufacture within the BBB, and co-peroxisomal-product peroxide acts as a signalling agent. LA and ALA cross the blood-brain-barrier (BBB), but are not significantly present in brain structural-tissue, likely being largely metabolised through peroxisomal pathways in astrocytes to substrate or energy. LA and ALA also have wider brain roles, including the following: LA-/ALA-oxidised products in injured brain tissue moderate immune function; as preferred substrates for LOX12/15; LA oxylipins the HODEs are the primary endogenous activators of PPAR gamma related peroxisomal activity; PPAR gamma and peroxide promote iNOS activity; iNOS-based NO production inhibits catalase assisting microglial oxidative function, in excess causing oxidative damage; further PPAR gamma moderates microglial function. LA oxylipin 13HODE overactivation of the PPAR gamma-related peroxisomal pathways results in imbalances in brain lipid composition; loss of LA; increased denovo lipid and cholesterol production; increased desaturation by SCD1 so increased mono- and polyunsaturated Omega-7 and Omega-9 fats including mead acid; intracellular lipid deposition including of cholesterol, increased oxidative stress; cardiolipin lipid species changes and imbalances; and mitochondrial dysfunction; which changes link to diseases of cognitive impairment, including depression and Alzheimer’s. Further changes in the LA, OA and PA desaturase products, so the lipid-membrane content including of cardiolipin, will change mitochondrial energetics. Exposure to LA oxylipins in the absence of sufficient lipid protective antioxidant capacity, makes mitochondria more susceptible to damage, including reduced cytochrome C-related ATP production, and results in release from cardiolipin of damaging LA-based oxylipins, including HODEs and 4HNE. Conversely ALA has surprising beneficial effects on brain function. A single “subchronic” injection of ALA into the bloodstream before induction of a stroke in mice reduced post-infarct ischaemic damage. Multiple pre-stroke ALA treatments improved survival by a factor of 3 at ten days, increased neurogenesis, enhanced brain plasticity, and were significantly antidepressant. The first casualties of nutrient-depleted pre-oxidised Omega-3:6 imbalanced diets are likely loss of IQ, abstract thought and crucially empathy, and arguably accompanied by increased aggression and territoriality. What is the future for individuals, nations and more widely humanity, if increasing numbers of humans are more aggressive and territorial, have falling IQs and depleted capacity for abstract thought and empathy? ‘The greatness of humanity is not being human but humane’ Gandhi.
![Figure 5: 1.5 “Effect of linoleic acid on insulin release. In pancreatic perfusion experiments, an equilibration period of 20 min preceded time 0. After a baseline period of 10 min, linoleic acid (10, 50, 100 and 150 µM) was administered for 30 min followed by basal medium (KRB) perfusion. The horizontal line indicates the presence of linoleic acid. Values are means ±SE (n = 4). Baseline effluent concentrations of insulin were 4172 ± 277, 1660 ± 352, 1910 ± 172, 1199 ± 127 pg/ml and 4271 ± 1739 pg/ml for the control group and 10, 50, 100 and 150 µM linoleic acid groups, respectively” from “The Natural PPAR Agonist Linoleic Acid Stimulated Insulin Release in the Rat Pancreas” [59] with very grateful thanks to the authors for the permission: Lai M, Teng T, Yang C. J Vet Med Sci. 2013 Nov; 75(11): 1449–1454. Diabetes Obes Metab. 2012 Nov;14 (11):1010-9](https://www.researchgate.net/profile/Robert-Brown-82/publication/308193954/figure/fig1/AS:408108619845635@1474312085647/Effect-of-linoleic-acid-on-insulin-release-In-pancreatic-perfusion-experiments-an_Q320.jpg)
![Figure 6: 1.6 “Effect of linoleic acid with or without glucose on insulin release in rats fed a high-fat diet for 13 weeks (HF 13). In pancreatic perfusion experiments, an equilibration period of 20 min preceded time 0. After a baseline period of 10 min, 100 µM linoleic acid with or without 10 mM glucose was administered for 30 min followed by a basal medium (KRB) perfusion. The horizontal line indicates the presence of linoleic acid and glucose. Values are means ±SE (n = 4). Baseline effluent concentrations of insulin were 4172 ± 277, 6463 ± 2373, 1199 ± 127, 3178 ± 318 pg/ml and 1626 ± 298 pg/ml for the control, linoleic acid (high-fat diet), linoleic acid (normal diet), linoleic acid with glucose (high-fat diet) and linoleic acid with glucose (normal diet) groups, respectively” from “The Natural PPAR Agonist Linoleic Acid Stimulated Insulin Release in the Rat Pancreas” [59] with very grateful thanks to the authors for the permission: Lai M, Teng T, Yang C. The Natural PPAR Agonist Linoleic Acid Stimulated Insulin Release in the Rat Pancreas. J Vet Med Sci. 2013 Nov; 75(11): 1449–1454. Diabetes Obes Metab. 2012 Nov; 14 (11):1010–9](https://www.researchgate.net/profile/Robert-Brown-82/publication/308193954/figure/fig3/AS:408108619845637@1474312086057/Effect-of-linoleic-acid-with-or-without-glucose-on-insulin-release-in-rats-fed-a_Q320.jpg)
![Fig. 31.4 A thought-provoking graph, which has been revisited and added to by Guyenet in a recent paper [41, 42]. The inclusion of the chimpanzee data by the author was indicational only; also, the chimp may have been captive. The graph titled "Linoleic Acid in US Body Fat, 1961-2008" is from his blog, with very grateful thanks to the author for the permission: Guyenet S. Whole Health Source Blog Seed Oils and Body Fatness-A Problematic Revisit http:// wholehealthsource.blogspot.com/2011/08/seed-oils-and-body-fatnessproblematic.html](https://www.researchgate.net/profile/Robert-Brown-82/publication/308193954/figure/fig9/AS:809224544215043@1569945574623/A-thought-provoking-graph-which-has-been-revisited-and-added-to-by-Guyenet-in-a-recent_Q320.jpg)
“Western”, Linoleic acid (LA) and refined carbohydrate calorie rich, Alpha Linolenic acid (ALA) deficient, nutrient depleted, highly oxidised inflammatory diets, combined with; lowered antioxidant capacity, heavily refined pre-oxidised food, and excess intake of easily oxidised sugars, amplifies natures signalling systems that trigger fat storage, putting fat deposition mechanisms into overdrive, leading to activation of oxidative stress related inflammation, and related adipose tissue macrophage immune signalling, so wider immune activation, mitochondrial dysfunction, insulin resistance, diabetes, metabolic syndrome and increased occurrence of comorbid “Western” diseases. Factors contributing to the risk of obesity are complex and multiple including; genetics; epigenetics; exercise; lifestyle; declining food quality; ability to sense combined with an inbuilt programming to hunger for, seek out and consume foods normally associated with a high nutrient content, namely plant reproductive tissue related foods that in nature are generally seasonal and are rich in; LA, sucrose, glucose, fructose, carbohydrates, antioxidants and minerals, but which in industrial-foods are often pre-oxidised, antioxidant depleted, and stripped during processing of their protective conutrients. In the context of a nutrient insufficient processed pre-oxidised Western diet, the consequence of high levels of the most common plasma LA oxylipins, the HODEs, and consequential activation of PPAR gamma related peroxisomal beta-oxidation pathways, is significant fat gain. LA oxylipins, the HODEs, are associated with a wide range of “Western” diseases in addition to obesity and diabetes. ALA equivalent but less researched oxylipins are in general protective. ALA followed by LA is the preferred substrate of LOX12/15, which in the absence of the competitive presence of ALA will produce LA HODEs. Further two oxidised Omega-6 AA products activate CB1 cannabinoid receptors, helping drive hunger and fat deposition. Mechanisms that may increase hunger also exist for the plant reproductive material related products fructose and glucose. Activation by inter-meal fasting, and or exercise, of PPAR alpha peroxisomal beta oxidation pathways is obesity protective, through activation of energy production pathways, increased antioxidant capacity, and diversion of inflammatory related LA peroxisomal beta-oxidation substrate to energy rather than repair, but not options chosen by many in a “Western” 24/7/365 culture of instant, cheap, highly refined, pre-oxidised LA rich food availability. Moderating LA intake, increased ALA intake, and intermittent energy deficit stress through exercise or short term fasting, combined with a nutrient dense diet, high in antioxidants and low in pre-oxidised products, particularly in the obese, may reduce inflammation, and oxidative stress, hence direct a greater balance of resources towards energy production rather than tissue repair and fat depostion pathways, and reduce mitochondrial damage and dysfunction, so limit adipose tissue gain and comorbid medical conditions, as evidenced in the use of intermittent short term fasting treatment in diabetes. Exercise without dietary change or calorie restriction, is not an automatic route to weight loss.
Peroxisomes are multifunctional organelles of great physiological importance and essential to development and health. They ‘harbour’ about 50 different enzyme activities. Peroxisomal malfunction has severe functional consequences, which manifest in a variety of health conditions, including Zellweger syndrome, with widespread and significant effects, including risk of early mortality, impaired cerebral development, functional issues, and deficient energy production. There are a wide range of peroxisomal activators with different activation capacities, some of which are common between PPAR alpha, delta, and gamma, peroxisome types, and some of which are applicable to specific PPARs. Peroxisomes and their products are underappreciated partners fundamental to healthy function of energy pathways, oxidative pathways, immune function including likely supporting macrophage phagocytosis, detoxification, and lipid including cholesterol production pathways. Peroxisomes produce medium fats (MCFs), acetyl coenzyme A (ACoA), and peroxide as lipid beta-oxidation by-products. The catalase enzyme located in peroxisomes produces catalase. Crucially, LA and ALA are the preferred beta-oxidation substrates of peroxisomes. Oxidised LA products, such as the HODEs, often the most common oxylipins in plasma, are the primary endogenous activators of PPAR gamma. MCFs and ACoA produced by PPAR gamma-related peroxisomal activation are generally directed by related gene activation to support tissue maintenance and repair, including production of lipids and cholesterol. The importance and functional relevance of PPAR gamma related peroxisomes is raised by the increased consumption of LA, within the context of a highly processed antioxidant-diminished nutrient deficient preoxidised western diet. PPAR alpha-related peroxisomally produced MCFs and ACoA are likely used to significantly assist fuel the brain and wider body during periods of glucose depletion, and are arguably more important than ketosis as a fuel source. Activation of PPAR alpha pathways, as well as assisting energy production pathways through related gene activation, results in diversion of lipid substrate away from maintenance pathways so reducing related oxidative stress and inflammation, as well as being associated with increased antioxidant protection. The main PPAR alpha activators include energy deficit stress, primarily exercise or fasting, giving them particular physiological relevance.
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) from fish and fish oils can protect against cardiovascular disease (CVD), which is still the most common cause of mortality and morbidity worldwide. To reduce CVD risk, integral lifestyle modifications, such as smoking cessation, moderate alcohol consumption, exercise, stress reduction, weight control, and diet, are needed. Evidence from several studies indicates that consumption of fatty fish and n-3 PUFAs reduces the risk of CVD and mortality. Several randomized trials and meta-analyses have shown that high doses (1.8–2.0 g/d) of n-3 PUFAs are associated with a modest reduction in risk of MI (−25 %) as a secondary prevention, but not in the risk of all-cause mortality. However, the clinical outcomes of n-3 PUFAs are unequivocal, because their effects appear to depend on optimal background treatments (such as statins or antiplatelet agents) and specific patient groups. Optimal cutoff dose has not been established for protective effects of n-3 PUFAs against CVD.
Fish and seafood are important sources for LC PUFAs, EPA and DHA. These fatty acids may be synthesised in the body from short-chain fatty acids, including ALA; however, the enzymes involved in this pathway are considered inefficient. This means direct EPA and DHA sources are an important part of the human diet. Unfortunately, due to unsustainability and fish toxin accumulation, there is a need for alternative sources of these beneficial fatty acids. Furthermore, it is necessary to find suitable options for vegetarians and vegans. Bioengineering of plant seed oils offers a prospective source for LC PUFA and may be acceptable to those who do not consume fish products. Furthermore, the development of algae aquaculture could provide a new source for high LC PUFA-containing fish oils, although production costs remain a major issue. Finally, introducing plant-derived omega-3 to livestock feeds may enhance the omega-3 LC PUFA content within meat and dairy products. These alternative sources hold the potential to meet the demand for fish and fish oils, while reducing the negative impact on fish stocks.
The mother provides various vital nutrients to the growing fetus during pregnancy. Maternal nutrient levels and fatty acids are critical for normal fetal growth and development. All fatty acids provide energy, but structural and metabolic functions primarily require the long-chain polyunsaturated fatty acids (LCPUFA). The biologically most active LCPUFA are docosahexaenoic acid (22:6, omega-3), eicosapentaenoic acid (20:5, omega-3), and arachidonic acid (AA, 20:4 omega-6) which are synthesized from their essential fatty acid precursors, alpha-linolenic acid (18:3, omega-3), and linoleic acid (18:2, omega-6). LCPUFA and their eicosanoid metabolites such prostaglandins and prostacyclins play a vital role in determining the length of gestation, initiation of labor, and placental growth and development. Storage of LCPUFA in maternal fat depots during early pregnancy serves as a sole source of LCPUFA for the growing fetus as the fetus has a limited capacity to synthesize LCPUFA due to lack of desaturases. Therefore, the amount of LCPUFA transported from the mother to fetus depends on maternal LCPUFA intake, metabolism, and placental uptake/transport of fatty acids. Accretion of maternal LCPUFA during pregnancy may reduce the risk of pregnancy complications such as preterm birth, intrauterine growth restriction, gestational diabetes mellitus, and preeclampsia. Maternal DHA and AA status positively influence fetal growth and brain development and also reduce the risk of developing non-communicable diseases in the offspring in adult life. This chapter describes the role of maternal LCPUFA in reducing the risk of adverse pregnancy outcomes.
Association of diet with human health and disease has been known for centuries. Because of humans’ geographical origin, the diet and its compositional variability are high among populations. Human diet, including fruits, vegetables, nuts, and other animal sources has rich sources of bioactive molecules and antioxidants. Majority of human diet derived from plant sources, which contains polyphenols including flavonoids and phenolic acids, accounted for 90 %, and most of them possess antioxidant activity. Oxidative stress owing to excess of free radicals not neutralized by antioxidant defense enzymes leads to several degenerative diseases including cardiovascular diseases (CVDs), diabetes, kidney disease, cancer, neurological disorders, obesity, and aging. Hence, antioxidant dietary supplements are the attractive strategy to overcome these diseases. Therefore, in this chapter, we have focused on the overview of diet, antioxidants, and function of various plant antioxidant constituents. Furthermore, we have illustrated the role of oxidative stress on various diseases including CVD, cancer, and diabetes. Beneficial effects of various antioxidants and other antioxidant system stimulators on in vitro and in vivo models are explained. Along with this, we provide notable evidences from clinical trials using antioxidants on various diseases.
Since the 1970s, there has been mounting evidence regarding the crucial role played by omega-3 fatty acids in the primary and secondary preventions of cardiovascular (CV) events. The omega-3 fatty acids of relevance are the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that are obtained from fish oils, and alpha-linolenic acid (ALA) from plant sources such as flaxseed oil. Research has proven their cardio-protective actions improve endothelial function, anti-inflammatory actions, inhibition of platelet aggregation, and regulation of influx and efflux of sodium and calcium channels and triglyceride lowering effects. They also play a role in prevention of heart failure by enhancement of cardiac remodelling. In this review, we discuss the CV benefits of omega-3 fatty acids, detailing their potential mechanisms of action in the prevention of CV mortality and sudden cardiac death. We have outlined the dosages recommended for therapy and have mentioned the reported side effects while presenting a collective overview of the recent randomized controlled trials and analysis on this subject, highlighting both results and limitations.
Psoriasis is a multifaceted autoimmune disorder associated with irregularities in the T-cell function. Activation of T-cell produces enriches amounts of biomarkers which are highly responsible for keratinocyte hyperproliferation in psoriasis. Among the diverse drug therapies available for treatment and management of psoriasis, administration of omega (ω) - 3 fatty acids (i.e., EPA and DHA) and their metabolites as alone or combination with other antipsoriatic drugs in dose-dependent manner results to inhibit proinflammatory mediators. Despites their potential benefits, these bioactive are associated with limitations like lipid peroxidation and improper bioavailability after oral and topical administration. To overcome these hiccups, emergence of nanomedicines has gained wider attention owing to their improved stability, optimum bioavailability and better efficacy against psoriasis treatment.
Omega-3 long-chain polyunsaturated fatty acids (n-3 PUFA) play an important role in the regulation of cellular membrane structure and function. They are essential for mammalian cells as they are not able to synthesize their precursor α-linolenic acid (18:3n-3), which can then be converted to more biologically active n-3 PUFA, EPA, and DHA, by a series of desaturation and elongation reactions. In recent years, it has been found that increased intake of n-3 PUFA is associated with a reduced risk of cardiovascular morbidity and mortality. Fish is the main dietary source of n-3 PUFA, although the concentration of n-3 PUFA is below the large amounts required to achieve the therapeutic benefits derived from EPA and DHA. This led to the development of formulations of n-3 PUFA containing high concentrations of purified EPA and DHA in a fixed, predefined ratio, with higher but different oral bioavailability and reasonable patient compliance to be used for dietary supplementation. This article reviews the pharmacokinetic profile of n-3 PUFA, including the digestion and bioavailability, tissular distribution (incorporation in plasma lipids, blood cells, and cell membranes), metabolism (β-oxidation, enzymatic biotransformation, synthesis of eicosanoids and other lipid mediators such as resolvins and protectins), and excretion. Factors that modulate oral bioavailability of n-3 PUFA (chemical and galenic formulations, food intake) are also analyzed. Additionally, the safety profile of n-3 PUFA, with particular attention to an increased bleeding risk, drug interactions, and contraindications, is reviewed.
Healthy aging is crucial for achieving a prolonged, disease-free life span in humans. In recent years, the shift in n-6: n-3 fatty acid ratio to as high as 20:1 from an ideal ratio of about 4:1 has been found to be a major cause of chronic inflammation and associated rise in cardiovascular disease, diabetes, cancer, osteoporosis, as well as autoimmune disorders in aging population. This chapter describes the role of n-3 fatty acids in conferring protection against cardiovascular disorders and age-related bone disorders such as osteoporosis. Fish oil fatty acids are believed to protect against inflammatory disorders and cardiovascular events through complex mechanisms including regulation of transcription factors involved in inflammation such as prostaglandins, leukotrienes, protectins, and resolvins by docosahexaenoic acid (DHA) and eicosapentanoic acid (EPA). Recent studies strongly suggest that DHA has a more potent and beneficial effects than EPA. Further, age-related bone loss in the elderly and in postmenopausal women is a global health concern. n-3 fatty acids are found to participate in bone remodeling through modulation of factors in the bone microenvironment. Rise in inflammation owing to increased inflammatory cytokine levels during aging contributes to the imbalance of cytokines such as TNF-α and IL-6 which are linked to the activation of osteoclasts and the loss of osteoblasts. The n-3 fatty acids DHA and EPA protect against age-related bone loss in animal models and in humans as evidenced by their positive effects on bone mineral density, bone turnover markers, as well as inflammatory markers. Further, an attempt has been made to describe the role of fish oil fatty acids in pain resolution and the importance of considering pain resolution parameters in randomized control trials.
... Biosynthetic pathway for omega-3 FAs production and information regarding sources. References: (Hegde et al., 2016;Innis, 2003). technological challenges (Alfio et al., 2021). ...
Background
Omega-3 fatty acids (FAs) are relevant commodities in the market since their important role in human wellbeing. As the worldwide demand is increasing, alternative sources and sustainable processes are needed to face the limited supply of the omega-3 FAs of fish origin. Microalgae provide a portfolio of biodiversity able to satisfy the quest for alternative sources and to match the need of sustainability for the production of these compounds.
Scope and approach
The review deepens the topic of sustainable production and supply by analyzing the current data available in scientific literature and providing a glance of the market of omega-3 FAs from different microalgal species. This was assessed in light of the technologies applicable to enhance and improve production. We analyzed and compared how traditional and innovative biotechnological approaches are exploited to maximize the ability of microalgae to produce omega-3 FAs, in particular eicosapentaenoic acid and docosahexaenoic acid (EPA and DHA).
Key findings and conclusions
This critical overview highlights that microalgal bioprospecting, combined with engineering approaches and with the study of the influence from the environment, can provide a reliable and sustainable alternative for omega-3 production. Unlocking the interdependence of these factors will play a key role for achieving the industrial scalability and standardization of the processes. Finally, the strategy to promote the consumer's acceptability of algae-based products will also be pivotal to substitute the current sources of omega-3 and therefore to address the sustainability challenges that Europe, as well as the rest of the world, is facing.
... Most ALA and LA can successfully cross the BBB and play a key role in the brain; for example, ALA followed by LA is the preferred peroxisomal beta-oxidation substrate. These depend on plasma availability and lipoprotein quantity and plasma lipid status that reflect dietary status in the brain [24,25]. Herein, we show the neuroprotective potential of ALA against Cd-induced neurodegeneration. ...
Alpha-Linolenic acid (ALA), an omega-3 polyunsaturated fatty acid, is extracted from plant sources and has been shown to be one of the anti-inflammatory and antioxidant agents. Herein, we revealed the molecular mechanism underlying the anti-inflammatory and antioxidant potential of (ALA), against cadmium in the adult mouse brain. We evaluated the neuroprotective effect of ALA (60 mg/kg per oral for 6 weeks) against CdCl2 (5 mg/kg)-induced oxidative stress, neuroinflammation, and neuronal apoptosis. According to our findings, ALA markedly reduced ROS production and nitric oxide synthase 2 (NOS2) and enhanced the expression of nuclear factor-2 erythroid-2 (Nrf-2) and heme oxygenase-1 (HO-1) in mice treated with CdCl2. Most importantly, the molecular docking study revealed that ALA allosterically decreases the overexpression of c-Jun N-terminal kinase (JNK) activity and inhibited the detrimental effect against CdCl2. Moreover, ALA suppressed CdCl2-induced glial fibrillary acidic protein (GFAP), nuclear factor-kappa b (NF-κB), and interleukin-1β (IL-1β) in the mouse brain. Further, we also checked the pro- and anti-apoptotic proteins markers such as Bax, Bcl-2, and caspase-3, which were regulated in the cortex of ALA co-treated mouse brain. Overall, our study suggests that oral administration of ALA can impede oxidative stress, neuroinflammation, and increase neuronal apoptosis in the cortex of Cd-injected mouse brain.
... Foods rich in Omega-3 and Omega-6 fatty acids are recommended in modern human diets as these two essential fatty acids are not synthesized in the human body, which could cause to nutritional imbalance causing inflammatory diseases [25]. Omega-3 fatty acids are primarily anti-inflammatory and omega-6 fatty acids are pro-inflammatory and thus the balance of these two fatty acids is important in human diet [26]. Jujube fruits could be a potential dietary source to balance these essential fatty acids in the human body. ...
The characteristics of fatty acids of 21 Chinese jujube varieties from three major production regions were studied. Twenty four fatty acids were identified by GC-MS and applying fatty acids methyl esters (FAMEs) method. The results showed that the fatty acids types and contents in different jujube cultivars were significantly different. Some of jujube cultivars had high palmitoleic acid content, as examples of ‘NYSLZ’ and ‘SZDZ’ with 11516 mg/100 g and 13632 mg/100 g, respectively. Most of jujube cultivars had high contents of oleic, linoleic and linolenic acids except ‘JDZ’, ‘JXZ’, ‘GZ’ and ‘ZHYMZ’. Meanwhile, the four cultivars of ‘YLZ’, ‘SYLZ’, ‘DHZ’ and ‘XHZ’ had a good balance of omega-3 and omega-6 fatty acids. The ‘MZ’, ‘SYLZ’, ‘NYSLZ’ and ‘DHZ’ cultivars contained a higher unsaturated/saturated fatty acid ratio than the other ones and the highest ratio was 180. In addition, the types and contents of fatty acids in jujubes from the different production areas varied. The hierarchical cluster analysis (HCA) and the linear discriminant analysis (LDA) revealed that different Chinese jujube cultivars were differentiated based on their fatty acid contents. The findings of this study illustrate that the nutritional profile of different Chinese jujube cultivars varies based on the geographical location and cultivation practices. The understanding of the nutritional profile of jujube cultivars can help food and agricultural industry identify right jujube cultivars with high nutritional contents, especially beneficial fatty acids.
... Shell eggs [1], consumed by people of almost all ages, are among the few food used worldwide, regardless of religion nor ethnicity [2]. The chicken egg is one of the awlessly preserved biological materials in nature [1], recognized as an excellent source of nutrients for humans [3], delectable and easy to digest [4]. A report by Attia et al. [5] showed that egg yolk contains nutritive and non-nutritive compounds that are bene cial to human health. ...
Background: The chicken egg is one of the nature’s flawlessly preserved biological products, recognized as an excellent source of nutrients for humans. Selenium (Se) is an essential micro-element that plays a key role in biological processes. Organic Se sources have shown many advantages over inorganic Se in poultry and can be produced biologically by microbial reduction of Se. Therefore, the possibility of integrating Se enriched bacteria as a supplement in poultry feed can provide an interesting source of organic Se, thereby increase egg Se concentration, improve oxidative stability and offer health-related advantages to humans. The objective of this study was to examine the effects inorganic and different organic Se sources on egg yolk colour, antioxidant profile, oxidative stability, and storage effect in relation to the treatments for fresh and stored egg yolk at 4±2 ⁰C for 14 days.
Results: The results reveals that dietary Se supplementation, especially the organic (ADS18 > Se-Yeast) sources influence (p < 0.05) egg yolk colour. Dietary inorganic Se and organic Se were noted to significantly improves egg yolk and breast meat antioxidants profile (total carotenoid and phenol content). There was a significant (p < 0.05) decrease in total cholesterol in fresh, stored egg yolk and breast muscle of Se treated groups compared with control. Whereas for breast muscle, only hens with organic Se supplementation (ADS18 > Se-Yeast) showed lower (p < 0.05) cholesterol compared to inorganic and control hens. The oxidative stability parameters of the eggs, breast and thigh muscle, and plasma showed a significant decrease (p < 0.05) in primary oxidation products (MDA) concentrations with hens supplemented with ADS18. However, the MDA content increased (p < 0.05) with an advanced storage period in egg yolk. It should be noted that, compared to inorganic Se and basal diets, egg yolk from hens fed with organic Se remain fresh for 2 weeks.
Conclusions: Dietary Se organic supplementation (ADS18 > Se-Yeast) improves egg yolk colour, antioxidant profile, and oxidative status of egg yolk and tissue. For egg enrichment and antioxidant properties, the source of supplemented organic Se is essential. Thus, ‘’functional eggs’’ enriched with organic selenium becomes possible to produced.
... The human diet must contain both omega-3 and omega-6 FAs in a balanced relation, because their imbalance can influence the development inflammatory disease. Omega-3 FAs are primarily anti-inflammatory, while omega-6 are pro-inflammatory [24]. Linolenic acid (C18:3n3) was the dominant omega-3 FA, and its highest content reached 43.2 mg/100 g in the 'LJZ' jujube cultivar pulp, followed by 29.2 mg/100 g in the 'BYZ' jujube. ...
Fatty acids (FAs) have important functions in the human body, and nutritional sources of rare FAs are of special interest. Here, we investigated the distribution of FAs in 21 different cultivars of Chinese jujube by conversion to FA methyl esters (FAMEs). All the tested jujube samples were harvested from one orchard with the same management. A total of 24 different FAs were found in 21 jujube cultivars, including both saturated and unsaturated FAs. Most of Chinese jujube cultivars contained high levels of total FAs, with a significant positive correlation for unsaturated FAs. Notably, we found a balanced content of essential omega-3 and omega-6 FAs, indicating that the Chinese jujubes have high nutritional value. However, the FA composition and content was significantly different among different cultivars. Finally, principal component analysis (PCA) and linear discriminant analysis (LDA) were conducted and most groups were separated clearly, which showed that FAs can be used to classify and differentiate the studied cultivars.
... PUFAs are functional elements of algal-membrane-lipids in the form of phospholipids and glycolipids and contribute in cell-signalling and physiology. Algae cultivation under low temperature condition allow high PUFAs content accretion and provides membrane fluidity [103,104], while high temperature favours opposite effects i.e. TAGs (functional lipid component for biodiesel production) accumulation in algae. ...
Current market trend and consumer's growing demand for healthy natural products have strengthened microalgae as an emerging source of nutrient rich natural food supplement. The constituents of food play a critical role in evolution of non-communicable disease and malnutrition. In this regard, microalgae based food products own positive health impacts and combating effects on non-communicable disease and malnutrition. These products appear as favourable sources of vitamins, minerals, proteins, functional lipids/poly unsaturated fatty acids and carotenoids etc. Present study highlights microalgae based poly unsaturated fatty acids such as omega-3 i.e. alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid and omega-6 and its biosynthesis, production, applications in public health and economic analysis associated with its production. Poly unsaturated fatty acids are considered as one of the promising sources of human's diet and their optimal proportion (omega-3 to omega-6; 1:1 to 1:4) is essential for prevention of non-communicable disease and other chronic diseases. Microalgae based poly unsaturated fatty acids functions as an alternative to fish oil and possess number of benefits in terms of taste, no/reduced toxins accumulation and veganism nature over animal based oils. Moreover, microalgae produce higher amount of omega-3 in contrast to animal based oils, for instance; Isochrysis galbana and Phaeodactylum tricornutum produce closely ≥2 folds higher eicosapentaenoic acid and Crytthecodinium cohnii produce nearly ≥6 folds higher docosahexaenoic acid than cod liver oil. In contrast, terrestrial plant-based poly unsaturated fatty acids lack eicosapentaenoic acid/docosahexaenoic acid. Thus, microalgae based poly unsaturated fatty acids represent compatible market for production of food and feeds products over fish and plant based poly unsaturated fatty acids. Current review provides critical examination of the literature investigating application of microalgae based functional lipids as dietary and nutraceutical supplement to improve public health. In addition, process economics and challenges have also been discussed in this paper.
Plant-based diets (PBDs) have been associated with a lower risk of cardiovascular disease (CVD). The aim was to investigate the predicted 5-year and 10-year risk of developing CVD in individuals following PBDs compared to regular meat-eating diets. This cross-sectional study included n = 240 middle-aged adults habitually consuming dietary patterns for ≥6 months: vegan, lacto-ovo vegetarian (LOV), pesco-vegetarian (PV), semi-vegetarian (SV) or regular meat-eater (RME) (n = 48 per group). Predicted 5-year and 10-year CVD risks were quantified using the Framingham Risk Equation and the Australian Absolute CVD risk calculator, respectively. Multivariable regression analysis was used to adjust for age, sex, smoking status, physical activity, alcohol use and BMI. Over three-quarters of the participants were women, mean age of 53.8 yrs. After adjustments for potential confounders, there was no difference in the predicted risk of CVD between regular-meat diets and PBDs, although crude analyses revealed that vegans had a lower 5-year and 10-year predicted risk of CVD compared to RMEs. SVs, PVs and LOVs had lower CVD risk scores, however, not significantly. Vegans had a favourable cardiometabolic risk profile including significantly lower serum lipid levels, fasting blood glucose and dietary fats and higher dietary fibre intake compared to RMEs. This was the first study to purposefully sample Australians habitually following PBDs. We found that PBDs do not independently influence the predicted risk of CVD, although PBDs tended to have lower risk and vegans had significantly lower cardiometabolic risk factors for CVD.
Marine lipids are recognized for their-health promoting features, mainly for being the primary sources of omega-3 fatty acids, and are therefore critical for human nutrition in an age when the global supply for these nutrients is experiencing an unprecedent pressure due to an ever-increasing demand. The seafood industry originates a considerable yield of co-products worldwide that, while already explored for other purposes, remain mostly undervalued as sustainable sources of healthy lipids, often being explored for low-value oil production. These co-products are especially appealing as lipid sources since, besides the well-known nutritional upside of marine animal fat, which is particularly rich in omega-3 polyunsaturated fatty acids, they also have interesting bioactive properties, which may garner them further interest, not only as food, but also for other high-end applications. Besides the added value that these co-products may represent as valuable lipid sources, there is also the obvious ecological upside of reducing seafood industry waste. In this sense, repurposing these bioresources will contribute to a more sustainable use of marine animal food, reducing the strain on already heavily depleted seafood stocks. Therefore, untapping the potential of marine animal co-products as valuable lipid sources aligns with both health and environmental goals by guaranteeing additional sources of healthy lipids and promoting more eco-conscious practices.
Marine fish are high in essential omega-3 fatty acids, which are important for human health. This study evaluated the effects of four extraction methods (soxhlet extrac-tion, SE; wet rendering, WR; acid silage, AS; microwave-assisted extraction, MAE) on the oil yield, physicochemical properties, fatty acid profile, and nutritional quality index (NQI) of pangus fish oil. The oil yield ranged from 13.50% to 21.80%, with MAE having the highest yield. Furthermore, MAE oil has the lowest free fatty acid (0.70%), peroxides (2.08 Meq/kg), and saponification (287.27 mg/g KOH) value. There were no significant differences (p> .05) in the refractive index and melting point of oils among extraction techniques. A total of 25 fatty acids were identified. However, the maximum PUFA, MUFA, and SFA recovery was observed in the SE (19.15 mg/100 g), MAE (7.99 mg/100 g), and AS (17.33 mg/100 g), respectively. In terms of NQI, SE had higher PUFA/SFA, HH, and LA/ALA ratios, while AS had higher EPA + DHA, n-3/n-6, AI, TI, and FLQ indices. Furthermore, the MAE approach yielded better ratios of n-3/n-6 and HPI index, whereas the WR method yielded a higher AI index. Therefore, MAE would be the most efficient method for extracting pangus fish oil by considering both technical feasibility and quality indices including extraction yield, best physical properties, oxidative stability, and fatty acid contents.
Red king crab (Paralithodes camtschaticus) is a large shelf species native to the Pacific Ocean. Due to its high commercial value, this species was introduced into the Barents Sea, where it has formed a new population that now supports a stable commercial fishery. Information on fatty acid profiles in different tissues of the Barents Sea P. camtschaticus is scarce. For this reason, the gonads of red king crabs collected at a coastal site in the Barents Sea during the summer were analyzed for fatty acid composition by gas-liquid chromatography. The proportions of total saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids in the ovaries of P. camtschaticus were 25.9 ± 2.0%, 22.5 ± 2.3%, and 51.6 ± 2.5%, respectively; in the testes, these levels accounted for 35.1 ± 5.7%, 19.1 ± 2.0%, and 45.8 ± 4.5%, respectively. Fatty acid profiles were similar in larger and smaller red king crabs and crabs with old and new shells. Concentrations of fatty acids were higher in ovaries compared to testes, reflecting higher reproductive efforts in female red king crabs. High levels of docosahexaenoic and eicosapentaenoic fatty acids detected in the ovaries of red king crabs from the Barents Sea indicate that these gonads can be a good alternative source for these fatty acids in the human diet and/or for extracting important fatty acids for use in the medical and pharmaceutical industries.
Microalgae have been increasingly considered as a sustainable “biofactory” with huge potentials to fill up the current and future shortages of food and nutrition. They have become an economically and technologically viable solution to produce a great diversity of high-value bioactive compounds, including n-3 polyunsaturated fatty acids (PUFA). The n-3 PUFA, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), possess an array of biological activities and positively affect a number of diseases, including cardiovascular and neurodegenerative disorders. As such, the global market of n-3 PUFA has been increasing at a fast pace in the past two decades. Nowadays, the supply of n-3 PUFA is facing serious challenges as a result of global warming and maximal/over marine fisheries catches. Although increasing rapidly in recent years, aquaculture as an alternative source of n-3 PUFA appears insufficient to meet the fast increase in consumption and market demand. Therefore, the cultivation of microalgae stands out as a potential solution to meet the shortages of the n-3 PUFA market and provides unique fatty acids for the special groups of the population. This review focuses on the biosynthesis pathways and recombinant engineering approaches that can be used to enhance the production of n-3 PUFA, the impact of environmental conditions in heterotrophic cultivation on n-3 PUFA production, and the technologies that have been applied in the food industry to extract and purify oil in microalgae and protect n-3 PUFA from oxidation.
Seaweeds are considered healthy and sustainable food. Although their consumption is modest in Western countries, the demand for seaweed in food markets is increasing in Europe. Each seaweed species has unique nutritional and functional features. The preparation of blends, obtained by mixing several seaweeds species, allows the obtaining of maximum benefits and ingredients with single characteristics. In this work, five seaweed blends, commercially available and produced under organic conditions in Europe, were characterized. The proximal composition included contents of ash (20.28–28.68% DW), proteins (17.79–26.61% DW), lipids (0.55–1.50% DW), and total carbohydrates (39.47–47.37% DW). Fatty acid profiles were determined by gas chromatography–mass spectrometry (GC–MS), allowing quantification of healthy fatty acids, namely n-3 and n-6 polyunsaturated fatty acids (PUFA), and calculation of lipid quality indices. Each blend showed a characteristic PUFA content in the lipid pool (35.77–49.43% of total fatty acids) and the content in essential and healthy n-3 PUFA is highlighted. The atherogenicity (0.54–0.72) and thrombogenicity (0.23–0.45) indices evidenced a good nutritional value of lipid fractions. As nutritional and environmentally attractive products, the consumption of the studied seaweed blends can contribute to a healthy lifestyle.
Gelidium corneum is a well-known agarophyte, harvested worldwide for its high agar quality. However, the species also exhibits an interesting nutritional profile, but with seasonal variations. Therefore, to evaluate the nutritional value of G. corneum, ash, crude protein, total lipids, and carbohydrates were analyzed at different times of the year. The heavy metals mercury, arsenic, lead, cadmium, and tin, as well as iodine were also measured. Finally, the seasonal antioxidant capacity of G. corneum extracts was evaluated. Our results indicate that the biomass is rich in protein (up to 16.25 ± 0.33%) and carbohydrates (up to 39.5 ± 3.29%), and low in lipids (up to 2.75 ± 0.28%), and especially in the summer, the AI, TI indexes, n-6/n-3 and h/H ratios (0.93, 0.6, 0.88 and 1.08, respectively) are very interesting. None of the contaminants exceeded the legally established limits, and the iodine values were adequate for a healthy diet. Finally, the antioxidant capacity is fair, with the DPPH ≤ 10.89 ± 1.46%, and ABTS ≤ 13.90 ± 1.54% inhibition, FRAP ≤ 0.91 ± 0.22 AAE.g −1 , and TPC ≤ 6.82 ± 0.26 GAE.g −1. The results show that G. corneum is an attractive resource, with potential use as food or as a food supplement.
Fish vary in their ability to biosynthesise long-chain polyunsaturated fatty acids (LC-PUFA) depending upon the complement and function of key enzymes commonly known as fatty acyl desaturases and elongases. It has been reported in Solea senegalensis the existence of a Δ4 desaturase, enabling the biosynthesis of docosahexaenoic acid (DHA) from eicosapentaenoic acid (EPA), which can be modulated by the diet. The present study aims to evaluate the combined effects of the partial replacement of fish oil (FO) with vegetable oils and reduced environmental salinity in the fatty acid composition of relevant body compartments (muscle, hepatocytes and enterocytes), the enzymatic activity over α-linolenic acid (ALA) to form n-3 LC-PUFA through the incubation of isolated hepatocytes and enterocytes with [1-14C] 18:3 n-3, and the regulation of the S. senegalensis fads2 and elovl5 in the liver and intestine. The presence of radiolabelled products, including 18:4n-3, 20:4n-3 and EPA, provided compelling evidence that a complete pathway enabling the biosynthesis of EPA from ALA, establishing S. senegalensis, has at least one Fads2 with ∆6 activity. Dietary composition prevailed over salinity in regulating the expression of fads2, while salinity did so over dietary composition for elovl5. FO replacement enhanced the proportion of DHA in S. senegalensis muscle and the combination with 20 ppt salinity increased the amount of n-3 LC-PUFA in hepatocytes.
Iron deficiency (ID) affects people of all ages in many countries. Due to intestinal blood loss and reduced iron absorption, ID is a threat to IBD patients, women, and children the most. Current therapies can efficiently recover normal serum transferrin saturation and hemoglobin concentration but may cause several side effects, including intestinal inflammation. ID patients may benefit from innovative nutritional supplements that may satisfy iron needs without side effects. There is a growing interest in new iron-rich superfoods, like algae and mushrooms, which combine antioxidant and anti-inflammatory properties with iron richness.
We report a novel stabilized emulsified formulation containing omega-3 fatty acid (ω-3 FA) and micronutrient that can be readily used for food fortification. The emulsification methodology for producing a stabilized formulation containing both ω-3 FA and micronutrients is described. The formulation was developed considering the human requirement of ω-3 FA and recommended daily allowance of important micronutrients. This formulation was characterized for physical appearance, pH, specific gravity, color measurement etc. Fatty acid analysis revealed formulations (2, 4 and 5 g/serve) were able to provide 500—1300 mg of alpha linoleic acid. Oxidative stability assessment (peroxide value, free fatty acid content) of the formulations showed, stability of the formulation as non-significant alterations were noted in these parameters when the formulations were compared with raw flaxseed oil. Rheological evaluation indicated formulation followed Non-Newtonian system with shear thickening behavior. Particle size was found to be between 673.83 to 798.76 nm and poly-dispersity index was between 0.438 to 0.681. Microscopic analysis by Cryo-SEM analysis of the formulation showed stable homogeneous nature of formulation. Stability of the formulations was confirmed by freeze-thawing, dilution test and emulsion stability index. Acute oral toxicity study as per OECD guideline showed safety of the formulations. Most importantly, in vivo bioavailability study of ω-3 FA confirmed better bioavailability of the metabolites of ω-3 FA i.e. eicosapentaenoic and docosahexaenoic acids in formulation treated group as compared to flax oil and comparable bioavailability to that of fish oil.
BACKGROUND
Omega‐3 common carp (OCC) raised by patented culture systems have higher level of n‐3 fatty acids and n‐3/n‐6 ratio than normal common carps (NCCs) from traditional culture system. Whether the patented farming system and modified fatty acid profile will influence OCC storage stability is unclear. This study aimed to expose the differences of post‐mortem quality changes between NCC and OCC.
RESULTS
NCC and OCC have similar rigor mortis patterns, only a higher level of lactic acid was observed in NCC after 96 h. Adenosine triphosphate (ATP) related compounds had no major differences, but slightly higher inosine monophosphate in OCC was found at 36 h. The K‐value, Ki‐value and Hx‐index demonstrated high cohesiveness (Pearsons two‐tailed, r = 0.968–0.984, P < 0.05) during storage, with statistically comparable (P > 0.05) temporal progress of change in NCC and OCC. The indices were lower in OCC than in NCC. Attenuation of myosin heavy chain in OCC was not as distinct as in NCC, coincided with its higher salt‐soluble protein level at 144 h. Before 96 h, thiobarbituric acid value (TBA), total viable count (TVC), cooking loss (CL), drip loss (DL), and hardness in NCC and OCC were similar. However, at 144 h, higher TBA, TVC, CL and DL while lower hardness in NCC than in OCC were observed. Principle component analysis showed good separation of NCC and OCC in biplot at 0 and 144 h.
CONCLUSION
Patented culture system has a slightly positive influence on post‐mortem quality of common carp. It can be used for producing OCC without compromising storage stability. © 2020 Society of Chemical Industry
Adipocytes play a central role in overall energy homeostasis and are important contributors to the immune system. Fatty acids (FAs) act as signaling molecules capable to modulate adipocyte metabolism and functions. To identify the effects of two commonly used FAs in Atlantic salmon diets, primary adipocytes were cultured in the presence of oleic (OA) or docosahexaenoic (DHA) acid. DHA decreased adipocyte lipid droplet number and area compared to OA. The increase in lipid load in OA treated adipocytes was paralleled by an increase in iNOS activity and mitochondrial SOD2-GFP activity, which was probably directed to counteract increase in oxidative stress. Under lipopolysaccharide (LPS)-induced inflammation, DHA had a greater anti-inflammatory effect than OA, as evidenced by the higher SOD2 activity and the transcriptional regulation of antioxidant enzymes and pro- and anti-inflammatory markers. In addition, DHA maintained a healthy mitochondrial structure under induced inflammation while OA led to elongated mitochondria with a thin thread like structures in adipocytes exposed to LPS. Overall, DHA possess anti-inflammatory properties and protects Atlantic salmon against oxidative stress and limits lipid deposition. Furthermore, DHA plays a key role in protecting mitochondria shape and function.
Linseed is a dietary source of plant-based ω–3 fatty acids along with fiber as well as lignans including secoisolariciresinol diglucoside (SDG). We investigated the reversal of signs of metabolic syndrome following addition of whole linseed (5%), defatted linseed (3%), or SDG (0.03%) to either a high-carbohydrate, high-fat or corn starch diet for rats for the final eight weeks of a 16–week protocol. All interventions reduced plasma insulin, systolic blood pressure, inflammatory cell infiltration in heart, ventricular collagen deposition, and diastolic stiffness but had no effect on plasma total cholesterol, nonesterified fatty acids, or triglycerides. Whole linseed did not change the body weight or abdominal fat in obese rats while SDG and defatted linseed decreased abdominal fat and defatted linseed increased lean mass. Defatted linseed and SDG, but not whole linseed, improved heart and liver structure, decreased fat vacuoles in liver, and decreased plasma leptin concentrations. These results show that the individual components of linseed produce greater potential therapeutic responses in rats with metabolic syndrome than whole linseed. We suggest that the reduced responses indicate reduced oral bioavailability of the whole seeds compared to the components.
Omega-3 fatty acids and carotenoids, which are known as representative high-value substances derived from microalgae, are being studied from various diatoms. Most of the diatoms contain fucoxanthin and omega-3 fatty acid. Fucoxanthin produced by diatom has been reported as bioactive compounds exhibiting strong antioxidant, anticancer and anti-inflammatory activities. However, the low growth rate and fucoxanthin content of diatoms are one of the big obstacles to the industrial application. In this study, indigenous marine diatom Achnanthidium sp. BS-001 was isolated for a candidate of fucoxanthin producer. Light intensity and temperature for the culture of Achnanthidium sp. BS-001 were optimized on PhotoBiobox. Optimization of silicate concentration for increasing
BS-001 biomass productivity was confirmed in F/2 medium with various concentration of sodium silicate. As a result, condition of light intensity, temperature, and silicate concentration for optimal cultivation were 150 μmol·m-2·s-1, 18℃ and 0.106 mM, respectively. Maximum biomass productivity reaches to 154.3 mg·L-1·day-1, and then the content of omega-3 fatty acids and fucoxanthin were 19.4 mg·g-1, 9.05 mg·g-1, respectively. These results indicate that Achnanthidium sp. BS-001 has the potential
to be used as a source of omega-3 fatty acids and fucoxanthin.
Introduction: Psoriasis management includes a variety of treatments including localized therapies and systemic treatments; however, many patients report inadequate clinical response and resistance to therapy. Currently there is no treatment algorithm that incorporates effective strategies to tackle the various barriers leading to resistance.
Areas covered: The authors evaluate the scope of resistance, the reasons it occurs, and provide the reader with strategies for overcoming resistance in both localized and systemic therapies for psoriasis.
Expert opinion: Refractory psoriasis involves modifiable and non-modifiable factors that warrant different approaches to maximize clinical response. Treatment-resistance to topical therapies may be due to poor adherence. Improving adherence involves incorporating patients’ treatment preferences, improving the physician-patient relationship, and simplifying treatment regimens. Treatment-resistance to systemic therapies can be due to non-adherence but can also be due to ineffective dosing, development of anti-drug antibodies, and severe disease that necessitates multiple drugs. After addressing non-adherence, strategies to maximize systemic therapies include increasing the dosage, combining treatments, drug switching and incorporating pharmacogenetics.
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) enriched eggs are popular for their enrichment of PUFAs, but their freshness and quality are prone to decline with time, particularly if storage conditions are not well maintained. Home storage is the last but a neglected important tach in eggs supply chain, but few studies are available on the egg storage in the home stage. This study aimed to evaluate the internal quality change of both n-3 PUFAs enriched and conventional eggs by simulating eggs stored at consumers’ home in refrigeration and under room temperature. The egg quality indices (Haugh unit, yolk index, weight, and albumen pH) were adopted and analyzed for both storage conditions. Wireless sensor network (WSN) was used for real-time monitoring of the temperature and humidity during storage. The results showed that temperature, humidity and time of storage all have an influence on the freshness of both n-3 PUFAs enriched and conventional eggs and there is no significant difference happened to n-3 PUFAs enriched eggs and conventional eggs. Refrigeration can decelerate the quality deterioration of both n-3 PUFAs enriched and conventional eggs and consumers should be educated about how to maintain the internal quality of eggs during home storage.
Identifying and addressing critical improvements in biomass, bioproduct and biofuel productivity is a priority for the nascent algae-based bioeconomy. Economic and sustainability principles should guide these developing improvements and help to unravel the contentious water-food-energy-environment nexus that algae inhabit. Understanding the biochemistry of storage carbon metabolism of algae to produce biofuels and bioproducts, can bring to light the key barriers that currently limit overall carbon efficiency, photosynthetic efficiency and ultimately guide productivity and commercial viability in the context of limiting resources. In the analysis reported here, we present different potential pathways for a conceptual algae biorefinery framework, with each pathway addressing one of the main identified barriers to future deployment. We highlight the molecular identification, in the form of an extensive literature review, of potential bioproducts that may be derived directly from both biomass and fractions produced through a conversion pathway, for three important commercially-relevant genera of algae, Scenedesmus, Chlorella and Nannochloropsis. We establish a relationship between each of the potential bioproducts, describe relevant conversion and extraction processes, and discuss market opportunities with values and sizes as they relate to commercial development of the products.
Omega-3 fatty acids provide significant health benefits and are a popular nutritional supplement in the nutraceuticals industry. Omega-3 fatty acids such as docosahexaenoic Acid (DHA) and eicosapentaenoic Acid (EPA) have been reported to improve heart health and mental health. In addition, DHA consumption has been tied to improvements in infant cognitive development. Therefore, high-purity DHA is a desired ingredient in the production of infant formula. The omega-3 oils originating from fish tend to have carcinogenic risks in addition to a bad odor. In recent years, the industry trend has shifted to producing these omega-3 fatty acids via microalgae species– making it a profitable time to enter the DHA production market. The proposed design is for a plant to cultivate the Schizochytrium cells in the upstream process, and then extract and purify the desired omega-3 fatty acid oils in the downstream process. The project proposal called for production of 881,800 lb DHA per year, but our plant has the capacity to produce 1,148,000 lb DHA per year at a competitive price of 775,600,000 and a ROI of 206.5%. The process itself begins with fermentation of the microalgae cells, starting with lab-scale fermentors, increasing in size to seed fermentors, and finally scaling up to production fermentor size. Schizochytrium sp. is the strain of heterotrophic microalgae, chosen for its ability to accumulate lipids in high concentration, and its ability to produce DHA triglyceride in high selectivity with respect to other omega-3 fatty acids. Following fermentation, extraction operations are carried out with a hexane solvent and bead mill to extract the crude oils. The hexane is then evaporated and recycled back to the bead mill. The purification process of the crude oil involves saponification of the triglycerides into fatty acid salts. Acetic acid is then added to convert the salts into the final docosahexaenoic acid product. The saponification and protonation reactions take place in Scheibel columns. The final DHA product is 98% pure by mass, and will be sent to a pack out station to be packaged into pharmaceutical grade drums for customers.
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