Omega-3 Fatty Acids in Alzheimer’s Disease Prevention Among Elderly Women: Mechanisms of Action, Clinical Evidence, and the Critical Role of Early Intervention

Fatty acids and bipolar disorder

Since the original American Heart Association (AHA) Science Advisory was published in 1996,1 important new findings have been reported about the benefits of omega-3 fatty acids on cardiovascular disease (CVD). Omega-3 fatty acids are obtained from two dietary sources: seafood and certain nut and plant oils. Fish and fish oils contain the 20-carbon eicosapentaenoic acid (EPA) and the 22-carbon docosahexaenoic acid (DHA), whereas canola, walnut, soybean, and flaxseed oils contain the 18-carbon α-linolenic acid (ALA). ALA appears to be less potent than EPA and DHA. The evidence supporting the clinical benefits of omega-3 fatty acids derive from population studies and randomized, controlled trials, and new information has emerged regarding the mechanisms of action of these nutrients. These are outlined in a recent Scientific Statement, “Fish Consumption, Fish Oil, Omega-3 Fatty Acids and Cardiovascular Disease.”2 See page e20 Large-scale epidemiologic studies suggest that people at risk for coronary heart disease (CHD) benefit from consuming omega-3 fatty acids from plants and marine sources. Although the ideal amount to take is not firmly established, evidence from prospective secondary prevention studies suggests that intakes of EPA+DHA ranging from 0.5 …

Rationale for different formulations of omega-3 fatty acids leading to differences in residual cardiovascular risk reduction

Colon cancer, which is the fourth most common cancer in the world, is one of the leading causes of cancer death in both men and women in the United States, Canada, Northern and Western Europe, Australia and New Zealand.1, 2 It is markedly less frequent in Asia, Africa and South America.1, 2 Therefore, it is a major public health problem. Migrant and temporal trend studies suggest that colon cancer is determined largely by environmental exposures, especially nutritional habits.1 Marked international differences in the incidence and mortality of colon cancer and increase of risk in populations migrating from low- to high-risk areas such as from Japan, China and the Philippines to the United States within 1 or 2 generations suggest that environmental factors, specifically dietary habits, rather than the genetic factors play an important role in the etiology of this cancer. This upward trend in incidences of colon cancer among Japanese immigrants in Hawaii and California compared to Japanese in Japan stimulated epidemiologists to investigate the reasons for this increase. Although the relationship between nutrition and cancer is complex and sometimes perplexing to nutritionists and to those who visualize carcinogenesis in terms of a specific carcinogen, it should be recognized that nutritional factors and diet may relate to cancer risk in several ways; first, food additives, contaminants, a particular dietary component, or products formed during food preparation may act as carcinogens, cocarcinogens and/or promoters; second, nutrient deficiencies and excesses may lead to biochemical/molecular alterations that may promote neoplastic processes; third, changes in the intake of selected macronutrients may induce metabolic, biochemical and molecular abnormalities that enhance cancer risk; and fourth, certain dietary constituents act as anticarcinogens or chemopreventives. During the last 3 decades, substantial progress has been made in understanding the relationship between dietary constituents and colon cancer risk. Fish oils are unique because they contain high levels of polyunsaturated omega-3 fatty acids (n-3 PUFAs) that are not present in vegetable oils or in saturated fats. Omega-3 fatty acids that are present in fish oil include docosahexaenoic acid (DHA; C22:6), eicosapentaenoic acid (EPA; C20:5) and docosapentaenoic acid (DPA; C22:5). Vegetable oils including corn oil and safflower oil contain high levels of linoleic acid (LA; C18:2). LA has the terminal double-bond 6 carbon atoms from the terminal (omega) methyl group of fatty acid, whereas DHA has the terminal double-bond 3 carbon atoms from the terminal (omega) methyl group of fatty acid (Fig. 1). Chemical structures of omega-3 and omega-6 fatty acids. Nutritional epidemiologic studies have provided evidence that dietary factors are important determinants of colorectal cancer in different populations worldwide. Cancer statistics in Japan for 2001 published by the Foundation for Promotion of Cancer Research indicate that there is an upward trend in age-adjusted mortality rates for colon cancer from 1955 to 1999.3 According to this report, the death rates due to colon cancer in Japanese men and women in 1955 were 2.9 and 3.0, respectively, whereas they increased to 14.7 and 9.8 in 1999. This upward trend in death rates due to colon cancer is mainly attributable to Westernization of Japanese food habits.3, 4 In addition, the report by the Foundation for Promotion of Cancer Research provided the data on the time trends in food consumption, which show increased dietary intakes of animal fat and meat and decreased consumption of whole grains from 1960 to 1999. For example, animal fat consumption in 1960 was about 25 g/day (per capita), whereas in 1999 it increased to about 58 g/day. Meat intake was increased from 19 to 78 g/day (per capita), whereas grain consumption decreased from 453 to 245 g/day during these years.3 The importance of types of dietary fat differing in fatty acid composition rather than total fat cannot be discounted because several preclinical studies using well-established colon cancer models strongly supported the notion that the colon tumor-promoting effect of dietary fat or lack of such effect depends on its fatty acid composition.5 A recent report by an expert panel assembled by the American Institute for Cancer Research/World Cancer Research Fund came to the scientific consensus that evidence for an association between the intake of saturated fat and/or animal fat and colon cancer risk is very strong.6 Continuing population studies revealed that diets particularly high in total fat, especially animal fat, are generally associated with increased risk of developing colon cancer, whereas high dietary fish oil or fish reduces this risk.7, 8 A recent ecologic study suggests that mortality data for colorectal cancer in 22 European countries, the United States and Canada correlate with the consumption of animal fat.7 That eating a diet rich in n-3 PUFAs may decrease the risk of colorectal cancer has been hypothesized in relation to fish and fish oil.7 Caygill and Hill et al.8 reported an inverse correlation between fish and fish oil consumption and colorectal cancer when expressed as a proportion of total or animal fat. This inverse relationship was significant for both male and female colorectal cancer, whether the intakes were in the current period or 10 years or 23 years before cancer mortality, It is noteworthy that these effects were only observed in countries with a high (> 85 g/caput/day) animal fat intake.8 Also, Mediterranean diet rich in olive oil and fish is associated with a low risk of colorectal cancer.9 On the basis of epidemiologic evidence, it is reasonable to suggest that diets high in saturated fats increase the risk of colorectal cancer, whereas diets high in fish and fish oil rich in n-3 PUFAs reduce the risk. Animal models have contributed significantly to understanding of the carcinogenesis process and to study the multiple environmental factors against the pathogenesis of colon cancer.10 Several studies have utilized these relevant animal models to investigate the modulation of colon carcinogenesis by nutritional and chemopreventive agents. These animal models include induction of colon tumors in rats by administration of aromatic amines such as 3,2′-dimethyl-4-aminobi-phenyl (DMBA); derivatives and analogs of cycacin, such as methylazoxymethanol (MAM), 1,2-dimethyl-hydrazine (DMH) and azoxymethane (AOM) in rats and mice of selected strains; direct-acting carcinogens of the type of alkylureas, such as methylnitrosourea (MNU) or N-methyl-N′-nitro-N-nitrosoguanidine (MNNG); and heterocyclic amines such as 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The spectrum of epithelial lesions induced in the colon by these agents is similar to various types of neoplastic lesions observed in the colorectum of humans. Azoxymethane (AOM), which is a potent inducer of carcinomas of the large intestine in various strains of male and female rats, has been used extensively by many investigators to induce colon tumors and to study the effects of nutritional factors and chemopreventive agents in colon carcinogenesis.10, 11, 12, 13, 14, 15, 16, 17 Colons of Fischer (F344) rats treated with AOM seem to have light and electron microscopic morphology as well as histochemical properties that are quite similar to that of humans and the biologic behavior of AOM-induced rat colon carcinomas is similar to that of human colon carcinomas.10, 18 Other characteristics of the human disease process reflected in the AOM rat model are the occurrence of both adenomas and adenocarcinomas.18 Also, aberrant crypt foci (ACF), which are recognized as early appearing preneoplastic lesions, develop in experimentally induced colon carcinogenesis in laboratory rodents as well as in the colonic mucosa of patients with colon cancer.19, 20 Recently, β-catenin-accumulated crypts were identified in the colonic mucosa at the early stages of AOM-induced colon carcinogenesis and are considered as early-appearing preneoplastic lesions.21 Therefore, ACF are now regarded as putative preneoplastic lesions for colon cancers and are used as biomarkers to evaluate potential chemopreventive agents against colon carcinogenesis.22 AOM treatment also induces oncogene mutations at codon 12 of K- and H-ras and increases in the expression of the ras family of protooncogenes have been causally associated with colon tumor development.23, 24 Enhanced ras oncogene expression has been observed in a variety of human colon tumors.25 AOM-induced colon tumors also demonstrate enhanced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression similar to human colon tumors.13, 26 Mutations in the tumor suppressor gene, APC, are known to be early events in the colon cancer process in humans and have been identified in patients with familial adenomatous polyposis, who have germline mutation in one of the APC alleles, and in sporadic colorectal cancer.27, 28 Evidence in humans thus implicates the APC suppressor gene as causal in large bowel carcinogenesis. Recent studies indicating the presence of APC mutation in AOM-induced colon tumors in rats strengthens the concept that these models are appropriate for human colon cancer studies.29 It has been increasingly apparent that β-catenin signaling pathway is closely associated with the development of colon cancer.30 Also, frequent mutations in the β-catenin gene are confirmed in AOM-induced colon tumors in rodent models.30 Furthermore, it has recently been indicated that the expression of nuclear β-catenin is correlated with the size of colon neoplasms.31 Because of similarities of histopathology of adenomas and adenocarcinomas, ACF and several molecular parameters between human colon tumors and AOM-induced colon tumors, it is indicated that the AOM model system and other chemically induced colon models appear to be appropriate colon cancer models. Recent progress in the area of molecular carcinogenesis has identified multiple molecular targets for the chemoprevention and nutritional modulation of colon cancer. The multiple intestinal neoplasia (Min) mouse, which carries a fully penetrant dominant mutation converting codon 850 of the murine APC gene from a lucine to a stop codon, is markedly different from that of patients with familial adenomatous polyposis (FAP) in which adenomas are found exclusively in the colon and duodenum, whereas in Min mouse adenomas are detectable in the small intestine and rarely in the colon. APCΔ716 knockout mice also develop numerous intestinal polyps at an early age.32 These are potential limitations of APCMin mouse and knockout models for testing agents for their potential chemopreventive properties against colon carcinogenesis. The development of strategies for prevention of colorectal cancer by dietary modification has been markedly facilitated by the use of relevant laboratory animal models, including carcinogen-induced colon cancer mimicking the neoplastic process that occurs in humans. Ample and consistent experimental evidence from preclinical efficacy studies conducted earlier have provided convincing evidence that not only the amount but also types of dietary fat differing in fatty acid composition are important factors in determining modulating effect of this nutrient in colon tumor development.33, 34, 35, 36 Studies conducted in our laboratory and those of others have consistently demonstrated that diets high in beef tallow, lard and corn oil (20–23% in the diet) significantly increased chemically induced colon carcinogenesis in F344 and Sprague-Dawley rats as compared to diets low (5%) in these fats.11, 33, 34, 35, 36, 37, 38 Additional studies conducted in our laboratory also demonstrate that male F344 rats fed diets containing 20% lard or 20% corn oil rich in n-6 PUFAs were more susceptible to 1,2-dimethylhydrazine-induced colon carcinogenesis compared with those fed diets containing 5% lard or 5% corn oil.38 Deschner et al.39 demonstrated that dietary n-3 PUFAs (fish oil) inhibits methylazoxymethanol (metabolite of azoxymethane)-induced focal areas of dysplasia and colon tumors, whereas n-6 PUFAs (corn oil) enhance colon tumorigenesis in rats. In a recent study, Chang et al.11 reported a protective effect of dietary fish oil against AOM-induced colon carcinogenesis in male Sprague-Dawley rats. High dietary fish oil significantly inhibited colon tumors as compared to high corn oil diet. In addition, colon tumor inhibition by fish oil diet was associated with lower levels of DNA damage in the distal colon compared with corn oil diet.11, 40 These studies provided evidence in preclinical models that diets containing high amount of saturated fat of animal origin or n-6 PUFAs had a greater colon tumor-enhancing effect than diets low in such fatty acids, whereas diets high in n-3 PUFAs had no such enhancing effect Further studies in our laboratory have evaluated the modulating effects of high dietary corn oil and safflower oil rich in n-6 PUFAs, olive oil high in monounsaturated fatty acid oleic acid, coconut oil high in medium-chain fatty acids such as lauric acid and fish oil during the postinitiation stage of AOM-induced colon carcinogenesis in male F344 rats.14, 37, 38, 41 Animals fed diets containing high corn oil or safflower oil (23.5%) had a higher incidence of colon tumors than did those fed diets low in fat (5%). By contrast, diets high in coconut oil, olive oil or menhaden fish oil had no such colon tumor-enhancing effect. The varied effects of different types of fat on colon carcinogenesis during postinitiation stage suggest that fatty acid composition is one of the determining factors in colon tumor promotion by a dietary fat and that the influence of types and amount of dietary fat is exerted mostly during the postinitiation phase of carcinogenesis.34, 41, 42 In this connection, it is interesting to note that in a phase 2 clinical trial of patients with colonic polyps, dietary fish oil supplements have in fact inhibited cell proliferation in the colonic mucosa.43 Thus far, progress has been made with regard to the relationship between dietary fat intake and colon cancer risk in that we know of the tumor-promoting effects of diets rich in n-6 PUFAs and saturated fatty acids and lack of such effects by n-3 PUFAs. However, it should be recognized that among the sources of dietary fat, animal fat with its high-saturated fatty acid content is by far the most important contributor, amounting to about 60%, to the Western diet. Importantly, dietary fat intake in the United States and Canada and other Western countries, where colon cancer rates are high, consists predominantly of a mixture of monounsaturated and polyunsaturated A recent in mice demonstrated that high dietary fat composition of the diet lesions in the colon of In of the of in colon cancer and because of potential properties of n-3 PUFAs, we have conducted a study to the effects of diets that contain rich in saturated fatty acids and to with the effects of fish oil during the different stages of colon carcinogenesis in male F344 preneoplastic lesions, were in fed the experimental diets for 23 and 38 which are putative preneoplastic lesions in the were observed at high in the colonic mucosa of patients with colon and of rats and mice treated with colon ACF and their are to be biomarkers of the effects of agents carcinogenesis in the colon. ACF were observed in the distal of rats. fed the diet a significantly greater of compared with those fed the corn oil or fish oil diet at time The incidence of aberrant foci was also higher in the diet group than in the or diet that administration of the diet significantly inhibits the and of preneoplastic lesions in the whereas the diet the of such Also, dietary significantly increased colon tumor incidence and when compared with the or Importantly, rats fed the diet incidence of colonic compared with incidences of and in rats fed the and Also, the of was significantly higher in fed the diet as compared to those fed the diet. the diet containing 20% fat in the of fish oil) induced tumors than diet containing the amount of total fat from This that both the type and the amount of fatty acids in the diet play a role in colon carcinogenesis. In evidence from preclinical studies is consistent with the epidemiologic The efficacy of dietary n-3 PUFAs including DHA and against colon carcinogenesis has also been in rodent models. et reported that administration of of DHA a for 4 and 12 significantly AOM-induced ACF in the colon. et also reported that administration of 1 of DHA a for 36 significantly AOM-induced colon tumor specifically in the and distal colon in male F344 rats. et compared dietary at LA at or LA at 5% against AOM-induced colon carcinogenesis in male rats. The indicate that the rats fed had a significantly lower colon tumor incidence and than those fed the LA diet. of tumors that the rats on diet had and more than those on the LA diet. Also, the content of in the colon tumors of LA diet group was higher than that in the colon tumors of the diet These suggest that its effect the modulation of in colon Several potential have been for colon cancer of types of dietary fat. Several studies indicate that diets high in saturated fatty acids and and n-6 PUFAs (corn oil or safflower oil) increase the of colonic acids, including acid and acid, whereas dietary fish oil high in n-3 PUFAs had no such enhancing epidemiologic studies demonstrated that populations who are on Western diet and at high risk for colon cancer high levels of acids have been to in a similar to induce cell proliferation and a in and act as in colon these suggest that acids that are by types of dietary fat may be important for in relation to colon tumor in by et dietary PUFAs may DNA and n-3 PUFAs may against colon carcinogenesis by DNA and/or enhancing DNA levels of AOM-induced DNA were in fish rats as compared to those fed corn oil rich in n-6 PUFAs. et and Chang et have also demonstrated that fish oil an increase in in the colon compared with corn rats. It is reasonable to that one of the by which n-3 PUFAs against colon carcinogenesis is in by the of DNA and by enhancing the of colonic Also, of fish oil or n-3 fatty acid increased and DHA levels in the of at the of n-6 fatty It has been that inhibition of colon carcinogenesis by DHA is the of a of a large of nuclear n-3 PUFAs effects in the colon the of nuclear of the nuclear are factors that cell and are studies to indicate that inducible nitric oxide synthase which is at the is in human colon and in chemically induced colon tumors of laboratory animal data also indicate that the of by is to carcinogenesis process and induces DNA lesions, thus in DNA and in the by family of also These data suggest a role for in tumor promotion and Studies conducted in our laboratory indicate that acid induces in intestinal with specific expression that one of the by which tumor including acids may an increase in expression of pathway that colon It is known that the fatty acid composition of is to diet. Studies conducted in our laboratory indicate that levels of dietary fish oil in rats increased the omega-3 fatty acids, DHA and in the colonic at the of omega-6 PUFAs such as linoleic acid and acid, the that the DHA and of fish oil the of by acid and linoleic acid in the Therefore, the types of dietary fat the fatty acid composition of colonic It is well that acid and of its including play an important role in the signaling pathway associated with cell proliferation and gene increase cell promote and of which are in tumor The by which n-3 PUFAs colon carcinogenesis are in of an important role in colon and who have in the of of rat intestinal epithelial have that of lead to the of high intake of saturated fat and omega-6 PUFAs acid from and 41 levels of have been observed in human colon tumors and chemically induced colon tumors in rodent and human colon levels of that are by Northern Recent have a between the potential of APC mutations and by that of the gene reduces the of tumors in mice for an by more than Additional evidence a role for from our which show a in colon tumors in rodents with Recent studies conducted in our laboratory have provided convincing evidence that an diet AOM-induced expression of and from acid in colon tumors of rats, whereas the diet inhibits the levels of In this study, administration of the diet of in the colon tumors, significantly higher levels than the corn oil diet or the diet 28 indicating higher This suggests that inhibition of the modulation of may be important for the of n-3 PUFAs to colon Also, colon tumors of fed the diet a lower than was observed in the colon tumors of rats fed the diet. The of these studies indicating that of in the tumors of fed the diet in to the diet inhibits and the tumor the that of lead to the of In colon tumors, the levels of may be to by proliferation and induction of and thus tumor A major that to be is which signaling are in of the These not only a between dietary fatty acids, and of colon but also molecular targets for colon cancer prevention by which n-3 PUFAs colon carcinogenesis. The potential and molecular events by n-3 PUFAs against colon carcinogenesis. The of molecular events by n-3 PUFAs include including and specific and factors including that cell and High dietary n-3 PUFAs by with the modification and of modulation of thus Recent studies from our laboratory have that high dietary n-6 PUFAs enhance of including that have been or in colon tumor whereas diet containing n-3 PUFAs to the of these a gene family of that play in signaling events and are in proliferation and include several with unique to the from the et reported that chemopreventive efficacy of dietary fish oil is associated with the alterations in colonic a that is by PUFAs may influence the of the which a of It is interesting that several have been to in The a of ras that is to the of in the of cell of are in the etiology of human colon It is also known that of from to is facilitated by a of closely including which is by It that inhibition of ras association of and neoplastic of Studies conducted in our laboratory have provided data to indicate that high dietary n-6 PUFAs increases expression in colonic tumors, whereas high dietary n-3 PUFAs appear to by with modification and of the modulation of thus Several have demonstrated against in both cell and laboratory animal in DNA have facilitated the of in promotion and of colon cancer. of is correlated with the development of certain of has also been to induce an effect that with and cell have recently that expression of was in colon tumors of rats than in colon Colon tumors from rats fed the diet containing high levels of n-6 PUFAs very low levels of whereas the tumors from fed the diet containing high amount of n-3 PUFAs did not of These correlate with colon tumor incidences by dietary n-3 and n-6 PUFAs. It appear that modulation of a significant role in n-3 colon tumor inhibition and Additional studies conducted in our laboratory have demonstrated that DHA inhibits of colon cancer in and induces we also the effects of DHA on the genetic of human colon cancer at the using DNA in gene expression due to DHA treatment was observed to be in the multiple signaling in the of cell and of DHA on cell and induction of were by an increase in the of several of family of and of such as and of several of these and factors the of the chemopreventive efficacy of DHA and other important n-3 PUFAs present in fish oil and thus colon cancer. Also, of these and factors provided several expressed biologic many of which suggest as molecular targets for by chemopreventive including nutritional is a major of and mortality in patients with cancer, including colorectal cancer. Several clinical studies have provided evidence for effects of fish oil administration in cancer during Omega-3 fatty acids have been to have effects on in cancer in patients with cancer is to and is associated with a time and of A fish nutritional has the potential to be a and of a fish oil preparation of and and a preparation in patients with 85 The of of the of which in the of of cancer patients and death from attributable to of of in cancer by and this may be one of the for inhibition of tumor Also, fish oil at a of during In on the basis of epidemiologic evidence from ecologic and it is reasonable to suggest that diets high in saturated fats increase the risk of colorectal cancer, whereas diets high in n-3 PUFAs not increase its risk. The studies both epidemiologic and evidence for the effects of diets rich in n-3 in the prevention of colorectal cancer. Also, recent clinical demonstrate effects of fish oil administration in cancer and during and studies have provided convincing evidence that colon tumor-promoting effect of dietary fat depends on its fatty acid that the composition of dietary fatty acids is more to colon cancer risk than is the total amount of fat. studies also demonstrate that a diet high in including saturated fats of animal origin as well as high dietary n-6 PUFAs had a higher potential to promote colon tumorigenesis than of a diet on amount of fat containing n-3 PUFAs. Although the by which diets high in saturated fats as those in Western and n-6 PUFAs promote colon carcinogenesis are not fully the studies conducted thus far indicate that increased levels of colonic acids, modulation of the influence on and the expression of by the types of dietary fat, especially n-6 PUFAs, may play a role in colon carcinogenesis. Further studies are to the role of n-3 PUFAs on the modulation of that are in colon and other types of cancer. The of prevention is to decrease the and mortality from colorectal cancer. and those of others suggest that nutritional prevention has the potential to be a major of colorectal cancer especially prevention in the are and in n-3 PUFAs be before they are for cancer Although there are no data to indicate and n-3 PUFAs should be for prevention of colorectal cancer, levels of dietary n-3 PUFAs should be consistent with the on epidemiologic studies of disease as by several These studies suggest that fish or as as g/day of fish the risk of Although a dietary for n-3 PUFAs not there is a that consumption of amount of fish in our on the epidemiologic studies may also reduce the risk of colorectal cancer. et has that the of n-6 PUFAs to n-3 PUFAs may be important for The varied risk for and several types of cancer among Mediterranean and Western European populations may at in be on the basis of n-6 to n-3 of and 10 in their on preclinical and epidemiologic studies on and et for a in the intake of linoleic acid and increase in the intake of n-3 PUFAs that a of 2 be for prevention of and that this is in Western countries for prevention of and and This may well be for the prevention of colorectal cancer in the Importantly, consumption of and is also for those in Western countries to reduce the risk of colorectal cancer. In the prevention of colorectal cancer in omega-3 fatty acids are in and of be It should be recognized that with nutritional supplements and/or diet modification may not be for prevention of colorectal cancer in patients such as those with polyposis and sporadic colon This to colon cancer is of importance as have not been fully in the high incidence or low of colorectal cancer. However, by diet modification as to the with chemopreventive agents that or the development of those which with and progress to and is an for prevention of colon cancer in these high-risk This is important when chemopreventive agents demonstrate significant efficacy but may effects at higher It is certain that colon cancer prevention be a significant of and in high-risk by molecular targets that or stop the process of carcinogenesis. there is a to clinical in patients with sporadic colon polyps using the n-3 diets in with a chemopreventive to the of events leading to The for preparation of the and studies on n-3 PUFAs in colon cancer prevention are supported by the Cancer Institute and

Tissue Omega-6/Omega-3 Fatty Acid Ratio and Risk for Coronary Artery Disease

Paola Bozzatello et al. [1] have done a comprehensive qualitative review of the potential use of long-chain polyunsaturated fatty acids in the prevention and treatment of mental disorders.[...].

Introduction: Acne is one of the most common skin problems affecting people worldwide, especially young individuals. Despite many years of research into the etiology of acne, its exact causes remain a subject of debate. In recent years, increasing scientific interest has focused on the role of diet in shaping skin health, including the influence of omega-3 and omega-6 fatty acids on the severity of acne symptoms. Objective: The aim of this study is to review the scientific literature regarding the relationship between a diet rich in omega-3 and omega-6 fatty acids and the reduction of acne. We will analyze available scientific evidence and attempt to determine whether dietary changes to increase the intake of these fatty acids may have a beneficial impact on skin condition and reducing the severity of acne symptoms. Results: Several studies suggest that a diet rich in omega-3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and relatively low in omega-6 fatty acids may be associated with a reduction in acne severity. Some clinical studies have shown that supplementation with omega-3 fatty acids can lead to a reduction in the number of comedones and inflammatory skin lesions in acne patients. Conclusions: Our literature review suggests that a diet rich in omega-3 fatty acids and lower in omega-6 fatty acids may be beneficial for individuals struggling with acne. However, further clinical research is needed to confirm these observations and better understand the mechanisms of action of fatty acids on skin health. In the meantime, a balanced diet rich in omega-3-containing foods such as fatty fish, nuts, and seeds is recommended as a potential adjunct to acne treatment.

The importance of omega-3 fatty acids for physical health is now well recognised and there is increasing evidence that omega-3 fatty acids may also be important to mental health. The two main omega-3 fatty acids in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have important biological functions in the CNS. DHA is a major structural component of neuronal membranes, and changing the fatty acid composition of neuronal membranes leads to functional changes in the activity of receptors and other proteins embedded in the membrane phospholipid. EPA has important physiological functions that can affect neuronal activity. Epidemiological studies indicate an association between depression and low dietary intake of omega-3 fatty acids, and biochemical studies have shown reduced levels of omega-3 fatty acids in red blood cell membranes in both depressive and schizophrenic patients. Five of six double-blind, placebo-controlled trials in schizophrenia, and four of six such trials in depression, have reported therapeutic benefit from omega-3 fatty acids in either the primary or secondary statistical analysis, particularly when EPA is added on to existing psychotropic medication. Individual clinical trials have suggested benefits of EPA treatment in borderline personality disorder and of combined omega-3 and omega-6 fatty acid treatment for attention-deficit hyperactivity disorder. The evidence to date supports the adjunctive use of omega-3 fatty acids in the management of treatment unresponsive depression and schizophrenia. As these conditions are associated with increased risk of coronary heart disease and diabetes mellitus, omega-3 fatty acids should also benefit the physical state of these patients. However, as the clinical research evidence is preliminary, large, and definitive randomised controlled trials similar to those required for the licensing of any new pharmacological treatment are needed.

The nematode Caenorhabditis elegans is a powerful model organism to study functions of polyunsaturated fatty acids. The ability to alter fatty acid composition with genetic manipulation and dietary supplementation permits the dissection of the roles of omega-3 and omega-6 fatty acids in many biological process including reproduction, aging and neurobiology. Studies in C. elegans to date have mostly identified overlapping functions of 20-carbon omega-6 and omega-3 fatty acids in reproduction and in neurons, however, specific roles for either omega-3 or omega-6 fatty acids are beginning to emerge. Recent findings with importance to human health include the identification of a conserved Cox-independent prostaglandin synthesis pathway, critical functions for cytochrome P450 derivatives of polyunsaturated fatty acids, the requirements for omega-6 and omega-3 fatty acids in sensory neurons, and the importance of fatty acid desaturation for long lifespan. Furthermore, the ability of C. elegans to interconvert omega-6 to omega-3 fatty acids using the FAT-1 omega-3 desaturase has been exploited in mammalian studies and biotechnology approaches to generate mammals capable of exogenous generation of omega-3 fatty acids.

In order to predict omega-6 and omega-3 fatty acids in the diet of humans, seventy-three pork back fat adipose tissue samples were measured with Raman spectroscopy directly on adipose tissue and on melted fat. Melted fat samples were, in addition, measured with Fourier transform infrared (FT-IR) spectroscopy. Gas chromatography analyses were conducted as the reference analysis. Partial least squares regression (PLSR) was used to calibrate and validate all models predicting omega-3 and omega-6 fatty acids contents from spectra. Omega-6 fatty acids in melted fat measured with FT-IR was predicted with a correlation coefficient (R) of 0.93 and a root mean square error of cross-validation (RMSECV) of 1.61% of the total amount of fatty acids. Raman spectra measured on melted fat gave a prediction of omega-6 fatty acids with R=0.97, and RMSECV=0.99% of total amount of fatty acids. Omega-6 fatty acids were predicted with R=0.94, and RMSECV=1.50% of the total amount of fatty acids using Raman spectra recorded on adipose tissue. For omega-3 fatty acids, the highest R=0.91, and lowest RMSECV=0.23% of the total amount of fatty acids were obtained from Raman spectra acquired on melted fat. FT-IR and Raman spectroscopy may be used as rapid, nondestructive methods to determine omega-6 and omega-3 fatty acids in melted fat. Raman spectroscopy can also be used directly on adipose tissue.

BackgroundThe level of omega-6 and omega-3 polyunsaturated fatty acids can affect many cellular systems and function via nuclear receptors or the bioactive lipid regulation of gene expression. The objective of this study was to investigate changes in the muscle transcriptome and the biological functions regulated by increased consumption of omega-3 and omega-6 fatty acids in the pig gluteus medius muscle.ResultsThe transcriptome of the gluteus medius muscle was studied for pigs subjected to either a control diet or a diet supplemented with linseed and rapeseed oil to increase polyunsaturated fatty acid content. Next-generation sequencing (NGS) was used to generate the muscle tissue transcriptome database pointing differentially expressed genes (DEG). Comparative expression analyses identified 749 genes significantly differing at least in the twofold of change between two groups of animals fed with divergent level of omega-3 and omega-6 fatty acids. The expression of 219 genes was upregulated, and the expression of 530 genes was downregulated in the group of pigs supplemented with omega-3 and omega-6 fatty acids in relation to control group pigs. Results of RNA-seq indicated a role of fatty acid in the regulation of the expression of genes which are essential for muscle tissue development and functioning. Functional analysis revealed that the identified genes were important for a number of biological processes including inflammatory response, signaling, lipid metabolism, and homeostasis.ConclusionsSummarizing, obtained results provide strong evidence that omega-6 and omega-3 fatty acids regulate fundamental metabolic processes in muscle tissue development and functioning.

Polyunsaturated omega-3 and omega-6 fatty acids are essential fatty acids that cannot be produced by the body itself and therefore must be provided through nutrition. Omega-6 and particularly omega-3 fatty acids have important roles in the organism, contributing to the maintenance and promotion of health. The optimal proportion of omega-6/omega-3 fatty acids is 2:1, or even better 1:1. They are involved in normal growth and development, play a role in the prevention of coronary and cardiovascular diseases, of diabetes mellitus, of arterial hypertension, arthritis and cancer. Omega-3 fatty acids mainly have an anti-inflammatory effect, but also act as hypolipidemic and antithrombotic agents. A potential role of omega-3 fatty acids is that of increasing physical performance. Their role in the physical activity refers on one side to the global health of athletes and on the other side to their anti-inflammatory effect, as high intensity physical exercise induces increased free-radical production and microtraumas, with the induction of an inflammatory status. The anti-inflammatory effect of these fatty acids manifests through an increased production of endogenous antioxidant enzymes, through decreasing the production of prostaglandins metabolites, decreasing the production of leukotriene B4, etc. They are also effective on reducing muscle pain post eccentric exercise and on decreasing the severity of bronchoconstriction induced by exercise, as well as improving pulmonary function variables. In conclusion it seems that supplementing diets with omega-3 fatty acids, apart from having benefic effects on health and on the prevention and management of certain affections, proves to be a beneficial for physical activity and athletic performance.

BackgroundWe aimed to explore the association and potential causality between polyunsaturated fatty acids concentrations and the risk of periodontal disease.Materials and methodsData were collected from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). Weighted logistic regression analysis and restricted cubic spline (RCS) analysis were used to analyse the associations of the concentrations of omega-3 and omega-6 fatty acids and the omega-6/omega-3 fatty acids ratio with the risk of periodontitis. E-value and propensity score matching (PSM) analyses were used for sensitivity analyses. In addition, two-sample Mendelian randomisation (MR) analyses were performed to assess the potential causal impact of the concentrations of those fatty acids on periodontitis risk.ResultsA total of 2462 participants from the NHANES were included. Logistic regression analysis revealed that high omega-3 fatty acids levels were negatively associated with the risk of developing periodontitis (P < 0.05), while the omega-6/omega-3 fatty acids ratio was positively associated with the risk of developing periodontitis (P < 0.05). There was no significant association between omega-6 concentrations and the risk of periodontitis. The findings mentioned above were confirmed by analysis following a 1:1 PSM. Furthermore, MR examination of the two samples indicated no possible causal link between the risk of periodontitis and the concentrations of omega-3 or omega-6 fatty acids or the ratio of omega-6 to omega-3 fatty acids (P > 0.05).ConclusionAlthough omega-3 fatty acids and the omega-6/omega-3 fatty acids ratio were associated with the risk of periodontitis in cross-sectional studies, the MR results did not support a causal relationship between them. Therefore, there is no indication that an increase in the omega-3 fatty acids concentration or a decrease in the omega-6/omega-3 fatty acids ratio may be beneficial for preventing periodontitis.

Inflammation-related reactive oxygen species (ROS) and reactive nitrogen species (RNS) are associated with the development of cancer. ROS and RNS can directly damage biomacromolecules such as proteins, DNA, and lipids. Lipid peroxidation, however, can result in reactive carbonyl species (RCS) that can also modify proteins and DNA. In contrast to an extensive literature on the modification of proteins and DNA from omega-6 fatty acids, there are few studies on RCS generation from other fatty acids, particularly omega-3 fatty acids, which are frequently consumed from the diet and diet supplements. Therefore, a comparison between omega-3 and omega-6 fatty acids has been conducted. LC-MS/MS analysis of carbonyl-dinitrophenylhydrazine (DNPH) standards yielded characteristic fragment ions. Autoxidation products of α-linolenic acid and linoleic acid were then derivatized with DNPH and analyzed by LC-MS/MS. The results showed that α-linolenic acid, an omega-3 fatty acid, generated more acrolein and crotonaldehyde than did linoleic acid, an omega-6 fatty acid. Omega-3 fatty acids might be easily degraded to smaller monoaldehydes or dicarbonyls. Omega-3 fatty acids have been considered as health improvement components for a long time. However, on the basis of the results presented here, use of omega-3 fatty acids should be re-evaluated in vivo for safety purposes.

Reliability and Validity of a Culturally Appropriate Food Frequency Questionnaire to Measure Omega-3 Fatty Acid Intakes in Midwestern African American Women of Childbearing Age