Role of omega-6 and omega-3 fatty acids in fetal programming

Maternal nutrition plays a critical role in fetal development and can influence adult onset of disease. Linoleic acid (LA) and alpha-linolenic acid (ALA) are major omega-6 (n-6) and n-3 polyunsaturated fatty acids (PUFA), respectively, that are essential in our diet. LA and ALA are critical for the development of the fetal neurological and immune systems. However, in recent years, the consumption of n-6 PUFA has increased gradually worldwide, and elevated n-6 PUFA consumption may be harmful to human health. Consumption of diets with high levels of n-6 PUFA before or during pregnancy may have detrimental effects on fetal development and may influence overall health of offspring in adulthood. This review discusses the role of n-6 PUFA in fetal programming, the importance of a balance between n-6 and n-3 PUFAs in the maternal diet, and the need of further animal models and human studies that critically evaluate both n-6 and n-3 PUFA contents in diets.     

Proper balance of omega-3 and omega-6 fatty acid supplements with topical cyclosporine attenuated contact lens-related dry eye syndrome

Essential fatty acids had been applied in the treatment of dry eye syndrome (DES), but the effects of different combinations of fatty acids have not been investigated. 360 long-term contact lens wearers were included in this double-blinded study. Omega-3 and omega-6 fatty acids were combined in different ratios and supplied to the participants that were randomly divided into six groups, and the effects of different essential fatty acids mixture on DES with or without topical cyclosporine were investigated. More than half of long-term contact lens wearers suffered from DES, which were found to be attenuated by oral supplement of properly balanced O3FA and O6FA fatty acid. The topical cyclosporine treatment considerably inhibited the production of cytokines compared to the cyclosporine negative groups, which further relieved DES. Proper balance of omega-3 and omega-6 fatty acid combination significantly alleviated contact lens-related DES.     

Effect of omega-3 fatty acid supplementation on the arachidonic acid:eicosapentaenoic acid ratio

STUDY OBJECTIVES: To determine the baseline arachidonic acid:eicosapentaenoic acid (AA:EPA) ratio in patients with coronary artery disease and healthy subjects, and whether supplementation of omega-3 fatty acids, administered as fish oil capsules, affects this ratio. DESIGN: Prospective, open-label trial. SETTING: University-affiliated cardiology clinic. SUBJECTS: Thirty patients with stable coronary artery disease (CAD) and 30 healthy subjects. INTERVENTION: All participants received omega-3 fatty acids 1.5 g/day for 4 weeks, followed by 3 g/day for an additional 4 weeks. MEASUREMENTS AND MAIN RESULTS: For each participant, a lipid profile was determined at baseline and after 4 weeks of treatment with each dose. Other laboratory results analyzed were serum AA:EPA ratios, high-sensitivity C-reactive protein (hs-CRP) levels, and blood glucose levels. Mean +/- SD baseline AA:EPA ratios were 39.6 +/- 19.0 in healthy subjects and 23.7 +/- 12.5 in patients with CAD. These ratios decreased significantly in both groups after treatment with 1.5 g/day of omega-3 fatty acids: 9.0 +/- 4.2 in healthy subjects and 10.3 +/- 8.8 in patients with CAD. After treatment with 3 g/day, the ratios were further reduced: 5.1 +/- 3.2 in healthy subjects and 4.9 +/- 2.6 in patients with CAD. Supplementation with omega-3 fatty acids did not significantly affect hs-CRP, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, or blood glucose levels. Triglyceride levels were not reduced in patients with CAD but were significantly decreased in healthy subjects (by 20% decrease with omega-3 fatty acids 1.5 g/day and by 32% decrease with 3 g/day). CONCLUSION: Treatment with omega-3 fatty acids significantly reduced AA:EPA ratios in both healthy subjects and in patients with stable CAD. The treatment had no effect on hs-CRP levels in either group, and it reduced triglyceride levels in healthy subjects but not in patients with CAD.     

Effects of omega-3, omega-6 and omega-9 fatty acids on vascular smooth muscle tone.

The comparative effects of omega-3, omega-6 and omega-9 fatty acids on vascular smooth muscle tone were investigated. Docosahexaenoic acid (1-255 microM) and eicosapentaenoic acid (31-255 microM) inhibited phenylephrine-induced contractions, (8-63%) and (20-65%), respectively, which were not altered by indomethacin, NDGA, or by removal of the endothelium. Linoleic acid (18:2n6) and arachidonic acid (20:4n6) also induced significant relaxation. Therefore, fatty acid-induced relaxation of the rat aorta is specific to polyunsaturated fatty acids, 20:5n3, 22:6n3, 18:2n6 and 20:4n6.     

Depression and serum adiponectin and adipose omega-3 and omega-6 fatty acids in adolescents

The purpose of the present study was to investigate for a possible relationship between depression and serum adiponectin and adipose tissue omega-3 and omega-6 PUFA. The sample consisted of 90 healthy adolescent volunteers from the island of Crete. There were 54 girls and 36 boys, aged 13 to 18. The mean age was 15.2 years. Subjects were examined by the Preventive Medicine and Nutrition Clinic of the University of Crete. Depression was assessed through the use of the Beck Depression Inventory (BDI) and the Center for Epidemiologic Studies Depression Scale (CES-D). Fatty acids were determined by gas chromatography in adipose tissue. CES-D correlated with dihomo-gamma linolenic acid (DGLA). Multiple linear regression analyses showed that BDI was negatively associated with eicosapentaenoic acid (EPA), while CES-D was positively associated with DGLA in adipose tissue. Serum adiponectin was not significantly associated with depression. The negative relationship between adipose EPA and depression in adolescents, is in line with findings of previous studies involving adult and elderly subjects, demonstrating negative relations between depression and adipose omega-3 PUFA. This is the first literature report of a relationship between depression and an individual omega-3 fatty acid in adolescents. The inverse relationship between adipose EPA and depression indicates that a low long-term dietary intake of EPA is associated with an increased risk for depression in adolescents.     

Formation of cyclic deoxyguanosine adducts from omega-3 and omega-6 polyunsaturated fatty acids under oxidative conditions

The discovery of the cyclic 1,N(2)-propanodeoxyguanosine adducts of acrolein (Acr), crotonaldehyde (Cro), and t-4-hydroxy-2-nonenal (HNE) as endogenous DNA lesions from lipid peroxidation has raised questions regarding the role of different types of fatty acids as sources for their formation. In this study, we carried out reactions at pH 7 and 37 degrees C with deoxyguanosine 5'-monophosphate and omega-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA), linolenic acid (LNA), and eicosapentaenoic acid (EPA); or omega-6 PUFAs, including linoleic acid (LA) and arachidonic acid (AA), each in the presence of ferrous sulfate. The formation of Acr, Cro, and HNE-derived 1,N(2)-propanodeoxyguanosine adducts (Acr-, Cro-, and HNE-dG) in the incubation mixture was determined by reversed-phase HPLC analysis. The results showed that Acr and Cro adducts are primarily derived from omega-3 PUFAs, although Acr adducts are also formed, to a lesser extent, from oxidized AA and LA. HNE-dG adducts were detected exclusively in incubations with AA. The kinetics of the formation of these adducts was determined during incubations for 2 weeks and 5 days. The rate of Acr adduct formation was about 5-10-fold that of Cro adducts, depending on the type of PUFAs, and the rate of formation of HNE adducts from AA was also considerably slower than that of Acr adducts. Unlike other cyclic adducts, the formation of Acr adducts was independent of types of PUFAs, but its yield was proportional to the number of double bonds in the fatty acid. Only one of the isomeric Acr adducts was detected, and its stereoselective formation is consistent with that observed previously in vivo. Two previously unknown cyclic adducts, one derived from pentenal and the other from heptenal, were also detected as products from omega-3 and omega-6 fatty acids, respectively. This study demonstrated the specificity for the formation of the cyclic adducts of Acr, Cro, and HNE and other related enals by oxidation of omega-3 and omega-6 PUFAs. These results may be important for the understanding of the specific roles of different types of fatty acids in tumorigenesis.     

Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acids

BACKGROUND: Crohn's disease is a chronic inflammatory condition affecting the gastrointestinal tract. Polyunsaturated omega-3 fatty acids given orally may reduce the secretion of proinflammatory cytokines and hereby downregulate the inflammatory process. AIM: To assess the effects of enteral fatty acids, in the form of Impact Powder (Novartis, Switzerland), as adjuvant therapy to corticosteroid treatment on the proinflammatory and anti-inflammatory cytokine profiles in patients with active Crohn's disease. METHODS: The proinflammatory and anti-inflammatory cytokines were measured in plasma from 31 patients with active Crohn's disease. Patients were randomized for oral intake of omega-3 fatty acid (3-Impact Powder) or omega-6 fatty acids (6-Impact Powder). Clinical and biochemical markers of inflammation were studied at baseline and after 5 and 9 weeks. RESULTS: Within the 3-Impact Powder group, no significant changes in concentrations of interleukin-6, interferon-gamma, monocyte chemoattractant protein-1, interleukin-2, interleukin-5 and interleukin-10, whereas a significant differences in concentration of interleukin-1beta and interleukin-4 were observed during therapy. Within the 6-Impact Powder group a significant changes in concentrations of interleukin-1beta, interleukin-6, interferon-gamma, monocyte chemoattractant protein-1, interleukin-2, interleukin-4, interleukin-5 and interleukin-10 were observed. CONCLUSIONS: The 3-Impact Powder showed immunomodulatory properties and might inhibit an increase of proinflammatory cytokines in contrast to the 6-Impact Powder.     

Pleiotropic effects of omega-3 fatty acids

Omega-3 fatty acids except for their effect on triglycerides levels have cardioprotective properties as well as antiarrhythmic properties.The pleiotropic effects of omega-3 fatty acids, also, include lowering of blood pressure and the favorable effect on endothelial function and high-density cholesterol levels. Furthermore, studies have showed their favorable action in subjects with dementia, Alzheimer's disease and learning disorders. In this paper, a review of the recent patents on omega-3 fatty acids will be presented.     

Bioequivalence of two omega-3 fatty acid ethyl ester formulations: a case of clinical pharmacology of dietary supplements

AIM

To evaluate the bioequivalence of two omega-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA) ethyl ester preparations, previously shown not to be bioequivalent in healthy subjects, with the objective of providing a guideline for future work in this area.

METHOD

A randomized double-blind crossover protocol was chosen. Volunteers with the lowest blood concentrations of n-3 LC-PUFA were selected. They received the ethyl esters in a single high dose (12 g) and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) blood concentrations were analyzed after fingerprick collection at intervals up to 24 h.

RESULTS

Differently from a prior study, the pharmacokinetic analysis indicated a satisfactory bioequivalence: for the AUC(0,24 h) 90% CI of the ratio between the two formulations were in the range for bioequivalence (for EPA 0.98, 1.04 and for DHA 0.99, 1.04) and the same was true for C_max and t_max (90% CI were 0.95, 1.14 and 1.10, 1.25 for EPA and 0.88, 1.02 and 0.84, 1.24 for DHA).

CONCLUSION

This study shows that, in order to obtain reliable bioequivalence data of products present in the daily diet, certain conditions should be met. Subjects should have low, homogeneous baseline concentrations and not be exposed to food items containing the product under evaluation, e.g. fish. Finally, as in the case of omega-3 fatty acids, selected doses should be high, eventually with appropriate conditions of intake.     

Pharmaconutrition with omega-3 fatty acids: status quo and further perspectives

Beneficial rapid onset effects of omega-3 fatty acids from fish oil on host defense compensatory fit into the comprehensive pathophysiology of critical illness. Because of balanced pro- and anti-inflammatory effects on a variety of host defense subsystems even septic patients had earlier recovery and improved survival. This review focuses in a compressed view on the beneficial aspects of omega-3 fatty acid supplementation on diverse organ functions, host defense and on balanced pro - and anti-inflammatory effects. Clinical impact of fish oil based pharmaconutrition during critical inflammation processes and immune response in humans is thoroughly discussed.     

Chronic risperidone normalizes elevated pro-inflammatory cytokine and C-reactive protein production in omega-3 fatty acid deficient rats

Prior clinical and preclinical studies suggest that omega-3 fatty acids negatively regulate pro-inflammatory signaling cascades, and that the atypical antipsychotic risperidone up-regulates omega-3 fatty acid biosynthesis. In the present study, we investigated the effects of chronic (40days) risperidone treatment (3mg/kg/day) on basal pro-inflammatory cytokine (interleukin-6, IL-6; tumor necrosis factor-alpha, TNFα) and C-reactive protein (CRP) production in control and n-3 fatty acid deficient rats. Relationships with erythrocyte polyunsaturated fatty acid composition were determined. Compared with untreated controls, untreated n-3-deficient rats exhibited significantly greater basal IL-6, TNFα, and CRP production. Following chronic risperidone treatment there were trends for greater IL-6, TNFα, and CRP production in controls, but these did not reach significance. In n-3-deficient rats, chronic risperidone normalized elevated IL-6, TNFα, and CRP levels. Erythrocyte arachidonic acid (20:4n-6) composition was positively correlated, and erythrocyte eicosapentenoic (20:5n-3) and docosahexaenoic acid (22:6n-3) inversely correlated, with plasma IL-6, TNFα, and CRP levels in untreated control and n-3-deficient rats, and these associations were not observed among risperidone-treated rats. The adrenic acid (22:4n-6)/arachidonic acid ratio, an index of elongase-mediated arachidonic acid biosynthesis, was reduced by risperidone in controls and elevated in n-3-deficient rats. These preclinical data demonstrate that chronic risperidone treatment normalizes constitutively elevated pro-inflammatory cytokine and CRP production in n-3 fatty acid deficient rats but not in controls, and that the mechanism is dissociable from n-3 fatty acid biosynthesis.     

Do omega-3 fatty acids help in depression?

There is an increasing number of studies assessing whether omega-3 fatty acids play a role in behavioural and mood disorders, particularly depression. Findings of this research have been highlighted in the media, and in recent reports by the Mental Health Foundation and the food charity Sustain. As a result of such raising of awareness, patients might ask their GPs and mental health professionals about taking omega-3 fatty acids as a treatment for depression. Here we assess whether omega-3 fatty acids have a role in the management of such individuals.     

Effects of omega-3 fatty acid supplementation on mood and emotional information processing in recovered depressed individuals

Beneficial effects of omega-3 fatty acids have been reported for several psychiatric disorders, particularly for depression. Association studies show a relationship between omega-3 intake and depression risk. Meta-analyses of clinical trials have shown a moderate effect of supplementation on depressive symptoms, but not on normal mood states. Few studies have investigated effects on cognition. The purpose of this study was to examine effects of omega-3 supplements on cognition and mood of recovered depressed individuals. Seventy-one participants were randomized to receive either omega-3 or placebo for four weeks in a randomized double-blind design. Results showed small effects of omega-3 supplementation on aspects of emotional decision-making and on self-reported states of depression and tension. Some of the effects were confounded by learning effects. No significant effects were observed on memory, attention, cognitive reactivity and depressive symptoms. While inconclusive, the present findings may indicate that omega-3 supplementation has selective effects on emotional cognition and mood in recovered depressed participants.     

Reduced auditory acuity in rat pups from excess and deficient omega-3 fatty acid consumption by the mother

Consumption of the nutrients omega-3 fatty acids (omega-3 FA) during pregnancy and lactation is considered beneficial to fetal and infant development. It may also reduce the incidence and severity of preterm births by prolonging gestational length. However several recent human and animal studies have reported that over-supplementation with omega-3 FA, especially in the form of fish oil, can have adverse effects on fetal and infant development and the auditory brainstem response (ABR). Our goal was to assess further the effects of omega-3 FA excess and deficiency during pregnancy and lactation on the offspring's auditory acuity as evidenced by their ABR thresholds. Female Wistar rats were given diets that were either deficient, adequate (control) or excess in omega-3 FA from day 1 of pregnancy through lactation. The offspring were ABR-tested at the postnatal age of 24 days. The rat pups in the Excess treatment condition had significantly elevated (worse) ABR thresholds, postnatal growth restriction, and a trend for increased postnatal mortality in comparison to the Control group. The Deficient group was intermediate. In conclusion, excess or deficient amounts of omega-3 FA during pregnancy and lactation in the laboratory rat adversely affected the offspring's auditory acuity. Postnatal thriving was also adversely affected. Consuming or administering large or inadequate amounts of omega-3 FA during pregnancy and lactation seems inadvisable because of the potential for adverse effects on infant development.     

Lipidomics reveals the dynamics of lipid profile altered by omega-3 polyunsaturated fatty acid supplementation in healthy people

Glycerophospholipids (GPs) and sphingolipids (SPs) are important lipid components in the body and play biological functions. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are important nutrients, and their supplements are commonly used for preventing some diseases. However, the effect of n-3 PUFAs on the human glycerophospholipidome and sphingolipidome is unclear. We used targeted lipidomics to study the GP and SP profile of healthy individuals after supplementation with n-3 PUFAs for 3, 7, 14 and 21 days. Fuzzy c-means clustering was used to cluster the lipid species into six classes reflecting different changed-content patterns after n-3 PUFA supplementation. Among the species with significantly changed content, lysophospholipids were the most sensitive; their content started to increase on day 3. The content of phosphatidylserines increased at a later stage. The content of most of the phosphatidylcholines and alkylphosphatidylcholines decreased on day 21. A correlation network analysis of lipid species suggested that some enzymes involved in the metabolism of lysophospholipids and phosphatidylserines were regulated by n-3 PUFAs. Levels of creatine kinase-MB (CK-MB), urea, glucose, triglycerides and total bilirubin were altered by n-3 PUFA at 21 days. Correlation analysis revealed that the level of CK-MB was negatively correlated with those of species in lysophosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine and phosphatidylserine classes, which were increased by n-3 PUFA supplementation. With the analysis in this work, we demonstrated the regular pattern of n-3 PUFAs on GP and SP metabolism, which provides a pharmacological basis for n-3 PUFAs for clinical application.     

Excess and deficient omega-3 fatty acid during pregnancy and lactation cause impaired neural transmission in rat pups

Omega-3 fatty acids (ω-3 FA) consumption during pregnancy and lactation is beneficial to fetal and infant growth and may reduce the severity of preterm births. Thus, scientists and clinicians are recommending increasingly higher ω-3 FA doses for pregnant women and nursing babies for advancing the health of preterm, low birth weight, and normal babies. In contrast, some studies report that over-supplementation with ω-3 FA can have adverse effects on fetal and infant development by causing a form of nutritional toxicity. Our goal was to assess the effects of ω-3 FA excess and deficiency during pregnancy and lactation on the offspring's neural transmission as evidenced by their auditory brainstem responses (ABR). Female Wistar rats were given one of three diets from day 1 of pregnancy through lactation. The three diets were the Control ω-3 FA condition (ω-3/ω-6 ratio  0.14), the Deficient ω-3 FA condition (ω-3/ω-6 ratio  0%) and the Excess ω-3 FA condition (ω-3/ω-6 ratio  14.0). The Control diet contained 7% soybean oil, whereas the Deficient diet contained 7% safflower oil and the Excess diet contained 7% fish oil. The offspring were ABR-tested on postnatal day 24. The rat pups in the Excess group had prolonged ABR latencies in comparison to the Control group, indicating slowed neural transmission times. The pups in the Excess group also showed postnatal growth restriction. The Deficient group showed adverse effects that were milder than those seen in the Excess group. Milk fatty acid profiles reflected the fatty acid profiles of the maternal diets. In conclusion, excess or deficient amounts of ω-3 FA during pregnancy and lactation adversely affected the offspring's neural transmission times and postnatal thriving. Consuming either large or inadequate amounts of ω-3 FA during pregnancy and lactation seems inadvisable because of the potential for adverse effects on infant development.