Influence Of Omega-3 Fatty Acids Research Articles

Long-chain polyunsaturated fatty acids and brain functions

Introduction and purpose. Long-chain ω-3 PUFAs such as DHA and EPA are often present in high amounts in algae and fish. DHA in particular is crucial for the proper progress and functioning of the cerebrum because it is the main structural component of ω-3 PUFA in the brain. This makes it an indispensable element of the phospholipids of the nervous membrane. The purpose of this article is to present the assistance of Omega-3 acids in the functioning of the nervous system. State of knowledge. The text discusses a literature review focusing on the impact of omega-3 fatty acids. Polyunsaturated fatty acids (PUFAs) are essential for overall health and have been extensively studied for their contributions to human wellbeing and disease management. Recent research indicates their effectiveness in preventing and treating various diseases. Omega-3 PUFAs have been identified as therapeutic agents, particularly in combating inflammatory conditions like cardiovascular and neurodegenerative diseases. Material and method. The aim of this article is to present the benefits of omega-3 fatty acids augmentation. We used publications outlining properties of polyunsaturated fatty acids on the brain, articles presenting the outcomes of polyunsaturated fatty acids were reviewed using the PubMed platform. The review included the keywords “Omega-3 fatty acids”, “DHA”, “EPA”, “PUFA”. Summary. The review managed to present the influence of Omega-3 fatty acids on brain development, aging and a useful addition to the treatment of diseases such as Alzheimer's and drug-resistant epilepsy. By receiving multiple studies, the author confronted various opinions of specialists regarding the approach to supplementation of PUFA. Additionally, the conclusion was that marine fish oils in the appropriate doses do not cause any serious side effects. Considering their broad positive effect on the nervous system, every person should consume them.

Evaluation of Omega-3 Effect as Adjuvant Therapy to Methotrexate on Alkaline Phosphatase Level in Iraqi Patients with Active Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a common inflammatory disease associated with many extraarticularfeatures. The aim: of the current study is to assess the influence of omega-3 fatty acids(EPA, DHA) on serum alkaline phosphatase in patients with active RA. A single blinded placebocontrolled clinical trial with 12 weeks follow up period at which 50 patients with active RAusing methotrexate were randomized into 2 groups to receive either omega-3 (1000 mg) capsulethree times daily or capsules prefilled with glucose as placebo and were evaluated at zero time(baseline) and after 12 weeks for alkaline phosphatase level in serum. In addition to twenty fivehealthy subjects as control group. The age of RA patients in omega-3 group ranged from 25-80years (50.36±2.46), whereas the age of RA patients in placebo group ranged from 35-68 years(50.08±1.84 ), while the age of apparently healthy subjects in control group where ranged from40-60 years (94.20±1.12). The RA disease activity was measured using disease activity score of28 joints(DAS28-ESR) and clinical disease activity index (CDAI). After 12 weeks of startingadjuvant treatment with either omega-3 or placebo, the results showed that there were nosignificant difference between the effect of omega- 3 and placebo on alkaline phosphatase level.In Conclusion, omega-3 significantly decreased alkaline phosphatase level in patient with activerheumatoid arthritis

Omega-3 fatty acids and metabolic partitioning of fatty acids within the liver in the context of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is now the most prevalent form of liver disease globally, affecting about 25% of the world's adult population. It is more common in those living with obesity, where it may affect as many as 80% of individuals. The aim of this article is to describe recent human studies evaluating the influence of omega-3 fatty acids on de novo lipogenesis (DNL) and hepatic fatty acid partitioning between incorporation into triacylglycerols (TAGs) and β-oxidation, to discuss the relevance of these effects in the context of NAFLD, and to provide an overview of the mechanisms that might be involved. The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease hepatic DNL and partition fatty acids away from TAG synthesis and toward β-oxidation. EPA and DHA affect multiple hepatic transcription factors resulting in down-regulation of the DNL pathway and upregulation of β-oxidation. The net result is decreased accumulation of hepatic TAG and lowering of circulating TAG concentrations. Human trials demonstrate that EPA and DHA can decrease liver fat in patients with NAFLD. Increased intake of EPA and DHA may reduce the likelihood of hepatic TAG accumulation and could be used to reduce liver fat in patients with NAFLD.

Perioperative omega-3 fatty acids for liver surgery: A meta-analysis of randomized controlled trials.

Introduction:The effect of perioperative omega-3 fatty acids for liver surgery remained controversial. We conducted a systematic review and meta-analysis to explore the influence of omega-3 fatty acids versus placebo in patients undergoing liver surgery.Methods:We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2020, and included randomized controlled trials (RCTs) assessing the effect of omega-3 fatty acids versus placebo for liver surgery. This meta-analysis was performed using the random-effect model.Results:Five RCTs were included in the meta-analysis. Overall, compared with control group for liver surgery, omega-3 fatty acids were associated with substantially reduced incidence of infection (odd ratio [OR]=0.56; 95% confidence interval [CI] =0.34–0.91; P = .02), but revealed no remarkable influence on complications (OR = 0.60; 95% CI = 0.29–1.24; P = .17), mortality (OR = 0.76; 95% CI = 0.06–9.37; P = .83), liver failure (OR = 0.72; 95% CI = 0.10 to 5.00; P = 0.74), biliary leakage (OR=1.24; 95% CI = 0.41 to 3.76; P = .70), bleeding (OR = 1.76; 95% CI = 0.63–4.95; P = .28), or ileus (OR = 0.39; 95% CI = 0.07–2.05; P = .27).Conclusion:Perioperative omega-3 fatty acids may be beneficial to reduce the incidence of infection after liver surgery.

Omega-3 Fatty Acids and Coronary Artery Disease: More Questions Than Answers.

Studies show that patients with elevated triglycerides and well-controlled LDL levels under statin therapy still have a significant residual risk of cardiovascular (CV) events. Despite many attempts to reduce triglycerides with different hypolipidemic drugs, no therapeutic option has given satisfactory results so far. The initial enthusiasm that omega-3 fatty acids can effectively reduce triglycerides and CV risk was replaced with skepticism when the first large clinical trials failed to show any benefit in primary or secondary prevention. However, the latest studies succeeded in showing a positive effect of omega-3 fatty acids on CV outcome in patients with hypertriglyceridemia. The largest benefit was reported in secondary but not primary prevention. Interestingly, the reduction in triglycerides in some of these studies was disproportionately low to the relatively high CV risk reduction, which could indicate some other effects of omega-3 fatty acids that go well beyond hypotriglyceridemic action. This includes blood pressure reduction, antithrombotic effect, improvement of inflammatory status, endothelial function, and insulin resistance. Investigations also reported a significant and positive influence of omega-3 fatty acids on the composition and stabilization of coronary atherosclerotic plaques in patients with and without previous CV events. In addition to insufficiently known mechanisms of action and conflicting results about the effectiveness of omega-3 fatty acids, the safety problems, which include increased prevalence of atrial fibrillation and hemorrhage, were also reported. The aim of this clinical review was to summarize the current knowledge regarding the use of omega-3 fatty acids in CV patients, particularly those with coronary artery disease, and to present an overview of key clinical trial data.

The Influence of Omega-3 Fatty Acids on Skeletal Muscle Protein Turnover in Health, Disuse, and Disease.

Ingestion of omega-3 fatty acids is known to exert favorable health effects on a number of biological processes such as improved immune profile, enhanced cognition, and optimized neuromuscular function. Recently, data have emerged demonstrating a positive influence of omega-3 fatty acid intake on skeletal muscle. For instance, there are reports of clinically-relevant gains in muscle size and strength in healthy older persons with omega-3 fatty acid intake as well as evidence that omega-3 fatty acid ingestion alleviates the loss of muscle mass and prevents decrements in mitochondrial respiration during periods of muscle-disuse. Cancer cachexia that is characterized by a rapid involuntary loss of lean mass may also be attenuated by omega-3 fatty acid provision. The primary means by which omega-3 fatty acids positively impact skeletal muscle mass is via incorporation of eicosapentaenoic acid (EPA; 20:5n−3) and docosahexaenoic acid (DHA; 22:6n−3) into membrane phospholipids of the sarcolemma and intracellular organelles. Enrichment of EPA and DHA in these membrane phospholipids is linked to enhanced rates of muscle protein synthesis, decreased expression of factors that regulate muscle protein breakdown, and improved mitochondrial respiration kinetics. However, exactly how incorporation of EPA and DHA into phospholipid membranes alters these processes remains unknown. In this review, we discuss the interaction between omega-3 fatty acid ingestion and skeletal muscle protein turnover in response to nutrient provision in younger and older adults. Additionally, we examine the role of omega-3 fatty acid supplementation in protecting muscle loss during muscle-disuse and in cancer cachexia, and critically evaluate the molecular mechanisms that underpin the phenotypic changes observed in skeletal muscle with omega-3 fatty acid intake.

Distinct Influence of Omega-3 Fatty Acids on the Plasma Metabolome of Healthy Older Adults.

Omega-3 polyunsaturated fatty acids (n3-PUFA) are well recognized for their potent triglyceride-lowering effects, but the potential influence of these bioactive lipids on other biological processes, particularly in the context of healthy aging, remains unknown. With the goal of gaining new insight into some less well-characterized biological effects of n3-PUFAs in healthy older adults, we performed metabolomics of fasting peripheral blood plasma collected from 12 young adults and 12 older adults before and after an open-label intervention of n3-PUFA (3.9 g/day, 2.7 g eicosapentaenoic [EPA], 1.2 g docosahexaenoic [DHA]). Proton nuclear magnetic resonance (1H-NMR) based lipoprotein subclass analysis revealed the expected reduction in total triglyceride (TG), but also demonstrated that n3-PUFA supplementation reduced very low-density lipoprotein (VLDL) particle number, modestly increased high-density lipoprotein (HDL) cholesterol, and shifted the composition of HDL subclasses. Further metabolite profiling by 1H-NMR and mass spectrometry revealed pronounced changes in phospholipids, cholesterol esters, diglycerides, and triglycerides following n3-PUFA supplementation. Furthermore, significant changes in hydroxyproline, kynurenine, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) following n3-PUFA supplementation provide further insight into some less well-recognized biological effects of n3-PUFA supplementation, including possible effects on protein metabolism, the kynurenine pathway, and glucose metabolism.

Studies into Slo1 K+ channels and their ligand docosahexaenoic acid in murine sepsis to delineate off-target effects of immunonutrition

AimsStudies on omega-3 fatty acids, including docosahexaenoic acid (DHA), reveal diverging results: Their intake is recommended in cardiovascular disease and major surgery, while evidence argues against use in septic patients. DHA mediates its blood-pressure-lowering effect through Slo1 channels that are expressed on cardiovascular and immune cells. We hypothesised that conflicting effects of immunonutrition could be explained by the influence of omega-3 fatty acids on systemic blood pressure or immune effector cells through Slo1. Main methodsThe effect of DHA on blood pressure was analysed in septic wild-type (WT) mice. Septic WT and Slo1 knockout (KO) mice were compared regarding survival, clinical presentation, haematology, cytokine release and bacterial burden. Cytokine expression and release of bone marrow derived macrophages (BMDM) from WT and Slo1 KO mice was assessed in response to LPS. Key findingsThe significant blood-pressure-lowering effect of DHA in healthy animals was blunted in already hypotensive septic mice. Septic Slo1 KO mice displayed moderately lower bacterial burden in blood and lungs compared with WT, which did not translate into improved survival. Slo1 KO BMDM presented lower IL-6 levels in response to LPS, an effect that was abolished in the presence of DHA. More importantly, the strong inhibitory effect of DHA on IL-6 release was also observed in Slo1 KO BMDM. SignificanceThe controversial effects of immunonutrition in sepsis are unlikely to be primarily explained by the influence of DHA on blood pressure or effects on immune response mediated through Slo1 channels.

Influence of omega-3 fatty acids on skeletal muscle protein metabolism and mitochondrial bioenergetics in older adults.

Omega-3 polyunsaturated fatty acids (n3-PUFA) are recognized for their anti-inflammatory effects and may be beneficial in the context of sarcopenia. We determined the influence of n3-PUFA on muscle mitochondrial physiology and protein metabolism in older adults. Twelve young (18-35 years) and older (65-85 years) men and women were studied at baseline. Older adults were studied again following n3-PUFA supplementation (3.9g/day, 16 weeks). Muscle biopsies were used to evaluate respiratory capacity (high resolution respirometry) and oxidant emissions (spectrofluorometry) in isolated mitochondria. Maximal respiration was significantly lower in older compared to young. n3-PUFA did not change respiration, but significantly reduced oxidant emissions. Participants performed a single bout of resistance exercise, followed by biopsies at 15 and 18 hours post exercise. Several genes involved in muscle protein turnover were significantly altered in older adults at baseline and following exercise, yet muscle protein synthesis was similar between age groups under both conditions. Following n3-PUFA supplementation, mixed muscle, mitochondrial, and sarcoplasmic protein synthesis rates were increased in older adults before exercise. n3-PUFA increased post-exercise mitochondrial and myofibrillar protein synthesis in older adults. These results demonstrate that n3-PUFA reduce mitochondrial oxidant emissions, increase postabsorptive muscle protein synthesis, and enhance anabolic responses to exercise in older adults.

Influence of Omega‐3 Fatty Acids Intake on Human Responsiveness to Ambient Air Pollution Exposure

Exposure to air pollution, including particulate matter and gaseous pollutants, is associated with respiratory and cardiovascular morbidity, such as vascular dysfunction, high blood pressure, cardiac dysrhythmia, and impaired pulmonary function. Eicosapentaenoic acid (20:5, n‐3; EPA) and docosahexaenoic acid (22:6, n‐3; DHA) are the primary beneficial omega‐3 fatty acids found in seafood and fish oil. Dietary consumption of EPA and DHA has been shown to confer protection to the cardiovascular system. This registered and IRB approved panel study is designed to investigate the relationship between dietary consumption of EPA and DHA and ambient air pollution‐induced adverse cardiovascular and pulmonary responses. Cardiovascular and pulmonary indices in healthy 25–55 year‐old subjects consuming at least 3 g/week of EPA and DHA from supplements and dietary sources for a period of 6 months prior to enrollment (High Group) will be compared to a control group (Low Group) with an intake of no more than 1 pill/month of fish oil supplement and 1 serving (4–6 oz)/month of ocean fish/shellfish during the previous 6 months prior to enrollment. Subjects will undergo a battery of tests over 5 2‐day sessions at the U.S. Environmental Protection Agency Human Studies Facility, with each 7 or more days apart. The following endpoints will be measured: blood pressure, heart rate variability, blood fatty acid levels, endothelial cell function, retinal microvascular diameter, and spirometry. Subjects will wear GPS and activity monitors overnight during visits in order to permit a quantitative assessment of individual exposure to pollutants measured using area air quality monitoring stations and satellite imaging data. We hypothesize that dietary consumption of EPA and DHA influences adverse cardiopulmonary responses to ambient air pollution exposure.Support or Funding InformationU.S. Environmental Protection Agency

Omega 3 Fatty Acids: Novel Neurotherapeutic Targets for Cognitive Dysfunction in Mood Disorders and Schizophrenia?

An increasing body of evidences from preclinical as well as epidemiological and clinical studies suggest a potential beneficial role of dietary intake of omega-3 fatty acids for cognitive functioning. In this narrative review, we will summarize and discuss recent findings from epidemiological, interventional and experimental studies linking dietary consumption of omega-3 fatty acids to cognitive function in healthy adults. Furthermore, affective disorders and schizophrenia (SZ) are characterized by cognitive dysfunction encompassing several domains. Cognitive dysfunction is closely related to impaired functioning and quality of life across these conditions. Therefore, the current review focues on the potential influence of omega-3 fatty acids on cognition in SZ and affective disorders. In sum, current data predominantly from mechanistic models and animal studies suggest that adjunctive omega-3 fatty acid supplementation could lead to improved cognitive functioning in SZ and affective disorders. However, besides its translational promise, evidence for clinical benefits in humans has been mixed. Notwithstanding evidences indicate that adjunctive omega-3 fatty acids may have benefit for affective symptoms in both unipolar and bipolar depression, to date no randomized controlled trial had evaluated omega-3 as cognitive enhancer for mood disorders, while a single published controlled trial suggested no therapeutic benefit for cognitive improvement in SZ. Considering the pleiotropic mechanisms of action of omega-3 fatty acids, the design of well-designed controlled trials of omega-3 supplementation as a novel, domain-specific, target for cognitive impairment in SZ and affective disorders is warranted.

The effect of omega-3 fatty acids on biomarkers of inflammation: a rapid evidence assessment of the literature.

Previous studies of omega-3 fatty acids report improved outcomes where inflammation is a key factor. The objective of this systematic review is to evaluate effects of omega-3s on inflammatory biomarkers. Randomized clinical studies that measured the influence of omega-3 fatty acids on inflammatory biomarkers were identified using a comprehensive search. Eligible studies were rated with the American Dietetic Association Evidence Analysis Manual and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process to examine study quality and risk/benefit. 112 studies were included. Over 65% reported statistically significant effects. The majority were scored as low risk of bias (high quality) and scored strong (cardiac populations and critically ill) to weak (Alzheimer's Disease, hypertriglyceridemia/diabetes, and obesity) on the risk/benefit ratio evidence for modulation of inflammatory biomarkers. There was inadequate data to determine a GRADE for inflammatory biomarker studies for some conditions (healthy individuals, rheumatoid arthritis, metabolic syndrome, renal disease, pregnancy, or children). Clinical literature on the effects of omega-3 fatty acids on inflammatory biomarkers contains mostly small sample sizes, is neutral to high quality, and report mixed effects. Larger studies examining dose and delivery are needed.

Influence of omega-3 fatty acids from the flaxseed (Linum usitatissimum) on the brain development of newborn rats.

The importance of essential fatty acids, in particular the omega-3 family, in the central nervous system development of newborns is well documented. The flaxseed (Linum usitatissimum) is considered one of the best vegetable sources of omega-3 fatty acids. The influence of omega-3 fatty acids from flaxseed on the brain development of newborn rats was evaluated. Pups of the F1 generation were obtained from 18 female Wistar rats divided in 3 groups (n=6), FG: fed with diet based on Flaxseed added with casein, CG: Casein, and MCG: Modified Casein supplemented with fibers and soybean oil. Newborn pups were weighted and submitted to euthanasia; brains were collected for evaluation of weight and lipid profile through gaseous chromatography. Significant increase in brain weight (39%) and relative brain weight (37%) was verified in pups from mothers fed with flaxseed diet. The omega-3 (n-3) fatty acids from the flaxseed were found in abundance in the diet made with this oleaginous and also significant increase in docosahexaenoic acid (DHA) (38%), as well as in total of omega-3 (n-3) fatty acids (62%). Maternal diet of flaxseed during pregnancy influences the incorporation of omega-3 fatty acid in the composition of brain tissue, assuring a good development of this organ in newborn rats.

INFLUENCIA DE LOS ÁCIDOS GRASOS OMEGA-3 DE LA LINAZA (LINUM USITATISSIMUM) EN EL DESARROLLO DEL CEREBRO DE RATAS RECIÉN NACIDAS

Abstract Objectives: The importance of essential fatty acids, in particular the omega-3 family, in the central nervous system development of newborns is well documented. The flaxseed (Linum usitatissimum) is considered one of the best vegetable sources of omega-3 fatty acids. The influence of omega-3 fatty acids from flaxseed on the brain development of newborn rats was evaluated. Material and methods: Pups of the F1 generation were obtained from 18 female Wistar rats divided in 3 groups (n=6), FG: fed with diet based on Flaxseed added with casein, CG: Casein, and MCG: Modified Casein supplemented with fibers and soybean oil. Newborn pups were weighted and submitted to euthanasia; brains were collected for evaluation of weight and lipid profile through gaseous chromatography. Results: Significant increase in brain weight (39%) and relative brain weight (37%) was verified in pups from mothers fed with flaxseed diet. The omega-3 (n-3) fatty acids from the flaxseed were found in abundance in the diet made with this oleaginous and also significant increase in docosahexaenoic acid (DHA) (38%), as well as in total of omega-3 (n-3) fatty acids (62%). Conclusion: Maternal diet of flaxseed during pregnancy influences the incorporation of omega-3 fatty acid in the composition of brain tissue, assuring a good development of this organ in newborn rats.

Los ácidos grasos omega-3 en la prevención de la enfermedad de Alzheimer

Introduction and objectives: omega-3 acids are polyunsaturated fatty acids that have to be provided in a preformed way to diet, being in oily fish which are in most. Omega-3 fatty acids are found in neuronal lipid membranes to a great extent, providing stability, and optimizing synaptic communication. A diet low in omega-3 acids, and this is a trend in Western eating habits in recent times, could be a risk factor for the development of cognitive disorders. This review attempts to assess the influence of omega-3 fatty acids in dementia (also referring to cognitive decline and mild cognitive impairment situation). Development: neurobiological, epidemiological and clinical data of most important publications in this regard are presented. Conclusions: a majority of epidemiological studies and some clinical trials found that a diet rich in omega-3 acids may decrease the incidence of dementia, could be correlated with a slowing of normal cognitive decline associated with age, or reduce the cognitive impairment in elderly patients diagnosed with mild cognitive impairment. However, currently available data do not support their utility to in established dementia. Frequent consumption of fatty fish is highly recommended, considering their intake as a supplement in the event that this does not happen. (Alzheimer. Real Invest Demenc. 2011;49:12-18)

Production of omega-3 polyunsaturated fatty acid concentrates: A review

Recent developments on the production of omega-3 fatty acid concentrates have been reviewed with an emphasis on the scientific articles published from 2000. At first, a description of the role of essential fatty acids in the organism and the influence of omega-3 fatty acids in human health is presented. An account of the review articles that have been published in previous years related to the production or isolation of omega-3 fatty acids is then provided. The publications that have appeared over the last 8 years have been reviewed under two groupings, one involving the production of omega-3 from fish, and the other involving the isolation from alternative sources. Fish is the major source of omega-3 fatty acids and the fish oil extraction processes have been considered firstly, then the fish oil refining processes are presented and finally the omega-3 concentration from fish oil. Some considerations on the stability of polyunsaturated fatty acids against hydrolysis and oxidation and the procedures to avoid it are also presented at the end of this review. Omega-3 polyunsaturated fatty acids are being used quite extensively in the food industry to obtain omega-3 enriched food products. Most of the commercial concentrates that can be found nowadays are the omega-3 ethyl ester derivatives. However, research is ongoing to obtain the more natural and better digestible triglyceride concentrates. We present here a review of the most recent advances, regarding the production of omega-3 concentrates from the very first raw material that contains them from which they should be extracted to the omega-3 concentrates stabilization. In between, a good number of different technologies that are being industrially applied, or still under investigation, are reviewed. One of the technologies with high expectation is supercritical fluid technology, and it finds a relevant place in the review here presented. Industries involved on innovation, require rapid overviews of the different possibilities open for production, and in that sense, this review is expected to be of interest.

Long-chain ??-3 fatty acid supply in pregnancy and lactation

Long-chain omega-3 fatty acids are essential for the developing fetus. Docosahexaenoic acid, the most important omega-3 fatty acid, is an important component of neural and retinal membranes, and rapidly accumulates in the brain during gestation and the postnatal period. Positive associations have been shown between maternal intake of fish, seafood and omega-3 fatty acids during pregnancy and/or lactation and visual and cognitive development. The review focuses on new findings by both observational and interventional studies on the influence of omega-3 fatty acids during pregnancy or lactation on gestation length and birth weight, preterm delivery, preeclampsia, maternal depression and infant visual function and neural development. Omega-3 fatty acids have been associated with reduced risk of cardiovascular and other diseases. Observational and interventional studies indicate a significant association with prolonging gestation and reducing the risk of preterm delivery both in low-risk and in high-risk pregnancies. Further benefits have been suggested for intrauterine growth restriction, preeclampsia and postpartum depression, but the evidence is inconclusive. Higher maternal docosahexaenoic acid intake both in pregnancy and lactation is associated with positive infant neurodevelopmental outcomes. Women of reproductive age should achieve an average dietary docosahexaenoic acid intake of at least 200 mg/day.

The effects of Omega-3 fatty acids on growth regulation of epithelial ovarian cancer cell lines

Objective. Omega-3 fatty acids (OM-3FAs) have been shown to possess anti-carcinogenic properties. We investigated the effect of OM-3FAs on epithelial ovarian cancer cell lines to determine if a growth suppressive effect existed and to gain a better insight on the potential molecular mechanisms that may be involved. Methods. Three epithelial ovarian cancer cell lines (SKOV-3 [p53 null], TOV-21G [wt p53] and OVCAR-3 [mutant p53]) and one immortalized ovarian surface epithelial cell line (IOSE-29 [wt p53]) were treated with OM-3FAs and evaluated for cellular proliferation (WST-1 assay), apoptosis (Annexin V-FITC/PI method) and VEGF expression (VEGF ELISA assay). Results. A statistically significant inhibitory effect under the influence of OM-3FAs was detected in all four cell lines. Apoptosis and VEGF down-regulation were either limited or not detected in the p53 null and mutant cell lines, SKOV-3 and OVCAR-3 respectively. Apoptosis and/or VEGF down-regulation was strongly evident in the wt p53 cell lines TOV-21G and IOSE-29. Conclusion. These data suggest that, under the influence of OM-3FAs, there are definitive growth suppressive mechanisms at work and that the biologic effects of OM-3FAs may in part be mediated by the p53 status.

Influence of omega-3 fatty acids on the growth of human colon carcinoma in nude mice

The present study investigated the influence of dietary omega-3 fatty acid supplementation on the growth of human colon carcinoma xenograft in athymic nude mice. Four diets were fed to evaluate the effect of levels and types of fat on colon tumor growth. Animals were maintained on a standard diet modified by addition of fats containing omega-3 and omega-6 fatty acids to represent high and low fat intakes for 53 days. The final mean estimated tumor weight for the high fat corn oil (24%) fed group was 2302 mg, whereas the low fat (8% corn oil) group was 1681 mg. The final mean tumor weight of the high fat menhaden oil fed group was 782 mg representing a 66% decrease in growth compared to the high fat corn oil group and a decrease of 54% compared to the low corn oil fed group. The high fat golden algae oil fed group resulted in a mean final tumor weight of 223 mg representing a 90% inhibition of tumor growth relative to the high fat corn oil fed group and 87% inhibition of growth compared to the low fat corn oil fed group. These findings indicate that dietary omega-3 fatty acids possess significant tumor suppressing properties and that the primary tumor suppressing fatty acid is docosahexaenoic acid. Histopathologic examination of control and treated tumors and expression array analyses (human cytokine and apoptosis arrays) support the tumor growth inhibition data and provide evidence for discussion of possible mechanisms for the observed growth inhibition.

Effects of docosahexaenoic acid and eicosapentaenoic acid on androgen-mediated cell growth and gene expression in LNCaP prostate cancer cells.

There is some epidemiological support for a protective influence of omega-3 fatty acids against prostate cancer. We wanted to explore whether omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) can affect androgen receptor function in prostate cancer cells. Our study showed that both DHA and EPA inhibit androgen-stimulated cell growth. Androgenic induction of prostate-specific antigen (PSA) protein was repressed by DHA and EPA in a dose-dependent manner. The mRNA levels of five androgen up-regulated genes, PSA, ornithine decarboxylase, NKX 3.1, immunophilin fkbp 51 and Drg-1, were decreased with DHA treatment in the presence of androgens. Transfection experiments using a DNA vector containing androgen-responsive elements demonstrated that both DHA and EPA could interfere with transactivation activities of the androgen receptor (AR). However, western blot analysis of AR protein showed that DHA and EPA treatments did not change AR expression levels. Interestingly, the proto-oncoprotein c-jun was increased by DHA treatment. A transient transfection found that forced expression of c-jun inhibited AR transactivation activity. Thus, this study found that the inhibitory effects of omega-3 polyunsaturated fatty acids on AR-mediated actions are due, at least in part, to an increase in c-jun protein.