Levels Of Omega-3 Polyunsaturated Fatty Acids Research Articles

Abstract WP430: Long Chain Polyunsaturated Fatty Acids, Cerebral Small Vessel Disease and Incident Dementia

Objective: Long-chain omega-3 polyunsaturated fatty acids (PUFAs) have been identified as a potential protective factor for vascular events and cognitive impairment. However, few prospective studies have so far explored the impact of PUFAs on dementia while simultaneously controlling for MRI-findings, such as cerebral small-vessel disease (SVD) and brain atrophy. Methods: Within a cohort of Japanese participants with vascular risk factors and free of dementia, we evaluated the association between PUFAs levels, MRI-findings at baseline, and incident all-cause dementia. Circulating plasma levels of omega-3 (ie, eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]) and omega-6 (ie, dihomo-γ-linolenic acid [DGLA], arachidonic acid [AA]) PUFAs were measured at baseline. Baseline brain MRI was used to determine SVD (lacunas, white matter hyperintensities and cerebral microbleeds) and atrophy (medial-temporal lobe atrophy and bicaudate ratio). Logistic regression analyses were used to estimate the cross-sectional association between tertile of each PUFAs and MRI-findings. Cox proportional hazards analyses were performed to estimate the longitudinal association between PUFAs and dementia, adjusting for age, sex, APOEε4, educational level, vascular risk factors, cerebrovascular events, estimated glomerular filtration rate, and MRI-findings. Results: In the 613 subjects (age: 67.3 ± 8.4 years, male: 59%), multivariable analyses adjusted for potential confounders showed that any PUFAs was not significantly associated with each of SVD. During the mean 7.5-year follow-up (range: 3-13), 48 subjects were diagnosed with dementia (Alzheimer’s disease:24; vascular dementia:18; mixed-type:4; other: 2). In multivariable Cox models adjusted for confounders, the relative risk of all-cause dementia was 0.42 (95%CI, 0.17-0.96, p=0.040) in the highest versus lowest tertile of DHA levels. However, no significant associations with dementia were observed for circulating EPA, EPA/AA ratio, or omega-6 PUFAs. Conclusions: Our results provide additional evidence of DHA may be associated with lower risk of dementia.

Omega-3 polyunsaturated fatty acids in treating non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial

& aims: Few clinical trials have addressed the potential benefits of omega-3 polyunsaturated fatty acids (PUFAs) on non-alcoholic steatohepatitis (NASH). We evaluated the effects of supplementation with omega-3 PUFAs from flaxseed and fish oils in patients with biopsy-proven NASH. Patients received three capsules daily, each containing 0.315g of omega-3 PUFAs (64% alpha-linolenic [ALA], 16% eicosapentaenoic [EPA], and 21% docosahexaenoic [DHA] acids; n-3 group, n=27) or mineral oil (placebo group, n=23). Liver biopsies were evaluated histopathologically by the NASH activity score (NAS). Plasma levels of omega-3 PUFAs were assessed as a marker of intake at baseline and after 6 months of treatment. Secondary endpoints included changes in plasma biochemical markers of lipid metabolism, inflammation, and liver function at baseline and after 3 and 6 months of treatment. At baseline, NAS was comparable between the groups (p=0.98). After intervention with omega-3 PUFAs, plasma ALA and EPA levels increased (p≤0.05). However in the placebo group, we also observed increased EPA and DHA (p≤0.05), suggesting an off-protocol intake of PUFAs. NAS improvement/stabilization was correlated with increased ALA in the n-3 group (p=0.02) and with increased EPA (p=0.04) and DHA (p=0.05) in the placebo group. Triglycerides were reduced after 3 months in the n-3 group compared to baseline (p=0.01). In NASH patients, the supplementation of omega-3 PUFA from flaxseed and fish oils significantly impacts on plasma lipid profile of patients with NASH. Plasma increase of these PUFAs was associated with better liver histology. (ID 01992809).

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The intake of polyunsaturated fatty acids especially omega-3 is projected to be way below the recommended intake in Kenya. Thus, there is need to find other sources of polyunsaturated fatty acids (PUFAs). This study screened for the lipid profile and levels of omega-3 PUFAs in jackfruit and explored the variation in lipid profile of jackfruit seeds in different areas and treatments. The extracted lipids were characterized and analysis done using gas chromatography. The lipid content was found to be 0.45 ± 0.24%, iodine number was 60.76 ± 3.25, saponification number was 353.65 ± 14.21, and levels of omega-3 and of omega-6 PUFAs were also found to be 9.94 ± 0.99% and 31.19 ± 0.82%, respectively. Boiling and drying of seeds were found to greatly decrease the levels of polyunsaturated fatty acids such omega-3 and omega-6 and thus, not suitable methods for processing or preservation of jackfruit seeds. Key words: Jackfruit, omega-3 polyunsaturated fatty acids, lipid profile.

Omega-3 polyunsaturated fatty acids and chronic obstructive pulmonary disease.

The aim of the present review was to summarize recent research developments relating omega-3 polyunsaturated fatty acids (PUFAs) and chronic obstructive pulmonary disease (COPD). COPD is a chronic inflammatory disease; hence, omega-3 PUFAs may have beneficial effects. At present, however, there are limited data available regarding the potential for omega-3 PUFAs to be used therapeutically in COPD. In 2012-2013, several observational studies have emerged, which demonstrate that circulating omega-3 PUFA levels in COPD are inversely associated with systemic inflammation and positively associated with clinical outcomes. To date, all interventions incorporating omega-3 PUFAs in COPD have used nutrient combinations, such that the specific effects of omega-3 PUFAs cannot be determined. Three clinical trials in COPD are underway, which use therapeutic doses of omega-3 PUFAs alone, with positive results beginning to emerge in 2014. Observational data support the hypothesis that omega-3 PUFAs may provide a therapeutic strategy for managing COPD. Several intervention trials using omega-3 PUFAs in COPD are underway, which will provide a substantive amount of new data to inform the field and allow evidence-based advice to be generated for patients with COPD in the near future.

Beneficial effects of omega-3 polyunsaturated Fatty acids in gestational diabetes: consequences in macrosomia and adulthood obesity.

Omega-3 polyunsaturated fatty acids (PUFAs) are increasingly being used to prevent cardiovascular diseases, including diabetes and obesity. In this paper, we report data on the observed effects of omega-3 PUFA on major metabolic disorders and immune system disruption during gestational diabetes and their consequences on macrosomia. While controversies still exist about omega-3 PUFA effects on antioxidant status regarding the level of omega-3 PUFA in diet supplementation, their lipid-lowering effects are unanimously recognized by researchers. Animal studies have shown that omega-3 PUFA contributes to the maintenance of the immune defense system by promoting the differentiation of T helper (Th) cell to a Th2 phenotype in diabetic pregnancy and by shifting the Th1/Th2 ratio from a deleterious proinflammatory Th1 phenotype to a protective anti-inflammatory Th2 phenotype in macrosomia and in adulthood obesity that results from macrosomia at birth. Based on the available evidence, international nutritional and food agencies recommend administration of omega-3 PUFA as triglyceride-lowering agents, for the prevention of cardiovascular disease risk and during human pregnancy and lactation. Furthermore, studies targeting humans are still required to explore application of the fatty acids as supplement in the management of gestational diabetes and inflammatory and immune diseases.

The Urgent Need to Re-Think Outside the ?Omega-3 Pufas? Box

Today, there is a growing controversy on the association of intake of omega-3 polyunsaturated fatty acids (PUFAs) and the onset of cardiovascular diseases (CVDs) in humans. Some studies suggest that the consumption of oily fish leads to increased levels of omega-3 PUFAs and thereafter a favourable cardiovascular prognosis. These views have been supported by epidemiological data evaluated by metaanalyses and they have been linked to higher levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Clinically, men who consume oily fish at least once a week had a 50 percent lower incidence of coronary heart disease (CHD) and sudden cardiac death (SCD). Mechanistically, though, we still do not know how omega-3 PUFAs work. Their postulated mechanism in preventing atherosclerosis could be through lowering the levels of triacylglycerol, preventing arrhythmias, decreasing platelet aggregation, or lowering blood pressure [1].

Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.

Abstract 13593: Lower Plasma Omega-6 Polyunsaturated Fatty Acid Level and Malnutrition in Acute Heart Failure Patients and Its Association With Worse Clinical Outcome

Backgrounds: Malnutrition was reported to be associated with poor clinical outcome in acute heart failure (AHF) patients. Plasma omega-6 (n-6) polyunsaturated fatty acids (PUFA) were parts of the essential fatty acids absorbed with intestine, and its absorption impairment could occur in right side of heart failure (HF). Thus, we aim to investigate whether the n-6 PUFA level could be a marker for malnutrition and a determinant of prognosis in patients with AHF. Methods: We examined 320 consecutive AHF patients who admitted to our institution between January 2013 and January 2014 from prospective registry. Patients with acute coronary syndrome and without complete data-set at admission were excluded. Finally, 284 patients were divided into two groups according to the plasma n-6 PUFA level as follows; Group A [lower plasma n-6 PUFA (dihomo-gamma-linolenic acid plus arachidonic acid) (below 163 μg/ml, the median), Group B [higher plasma n-6 PUFA (above 163 μg/ml) level] at admission. Adverse events were defined as worsening HF and death. Results: During a mean period of 231 days, adverse events were occurred in 78 patients (27 %). Group A had higher incidence of adverse events compared with group B (35% vs 20%, P<0.01). Group A had lower blood pressure, hemoglobin, plasma omega-3 (n-3) PUFA levels, higher age and serum creatinine level on admission than group B. Regarding right HF sign, group A had higher prevalence of jugular vein distention (P=0.04), hepatomegaly (P<0.01) and higher bilirubin level (P<0.01) than group B. Furthermore, group A had lower serum total cholesterol (P<0.01), triglyceride (P=0.02), and albumin (P<0.01) levels as malnutrition than group B. In multivariate Cox proportional hazards model, lower plasma n-6 PUFA level (HR 1.62, 95% CI 1.01-2.65), higher serum creatinine (HR 1.83, 95% CI 1.02-3.59), and higher plasma BNP levels (HR 1.60, 95% CI 1.02-2.57) were independent determinants for adverse events, among variables including age, blood pressure, hemoglobin, plasma n-3 PUFA, serum albumin levels. Conclusions: Lower plasma n-6 PUFA level was an independent determinant for adverse events in association with right HF sign and malnutrition, suggesting plasma n-6 PUFA could be a potential surrogate marker for clinical outcome in AHF patients.

Low plasma eicosapentaenoic acid levels are associated with elevated trait aggression and impulsivity in major depressive disorder with a history of comorbid substance use disorder

Major depressive disorder (MDD) is associated with low levels of omega-3 polyunsaturated fatty acids (PUFAs), holding promise for new perspectives on disease etiology and treatment targets. As aggressive and impulsive behaviors are associated with low omega-3 PUFA levels in some clinical contexts, we investigated plasma PUFA relationships with trait aggression and impulsivity in patients with MDD. Medication-free MDD patients (n = 48) and healthy volunteers (HV, n = 35) were assessed with the Brown-Goodwin Aggression Inventory. A subset (MDD, n = 39; HV, n = 33) completed the Barratt Impulsiveness Scale. Plasma PUFAs eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachidonic acid (AA, 20:4n-6) were quantified and ln-transformed to mitigate distributional skew. Ln-transformed PUFA (lnPUFA) levels were predictors in regression models, with aggression or impulsivity scores as outcomes, and cofactors of sex and diagnostic status (MDD with or without a history of substance use disorder [SUD], or HV). Interactions were tested between relevant PUFAs and diagnostic status. Additional analyses explored possible confounds of depression severity, self-reported childhood abuse history, and, in MDD patients, suicide attempt history. Among PUFA, lnEPA but not lnDHA predicted aggression (F1,76 = 12.493, p = 0.001), and impulsivity (F1,65 = 5.598, p = 0.021), with interactions between lnEPA and history of SUD for both aggression (F1,76 = 7.941, p = 0.001) and impulsivity (F1,65 = 3.485, p = 0.037). Results remained significant when adjusted for childhood abuse, depression severity, or history of suicide attempt. In conclusion, low EPA levels were associated with aggression and impulsivity only in patients with MDD and comorbid SUD, even though in most cases SUD was in full sustained remission.

Effects of Heavy Metal Pollution on Omega-3 Polyunsaturated Fatty Acids Levels In Tilapia Fish from Winam Gulf of Lake Victoria

Winam Gulf is facing major pollution threats from anthropogenic input of pollutants such as heavy metals and agrochemical residues. This has deleterious effects on flora and fauna in the lake and consequently the quality of omega - 3 polyunsaturated fatty acids (PUFAs) which have numerous health benefits in humans. In addition, heavy metal bioac- cumulation in fish poses a threat to human health. The major objective of the study was to establish whether there is a cor- relation between the heavy metal pollutants and the levels of omega - 3 PUFAs in fish. Levels of heavy metals - lead, cadmium, Zinc and chromium in sediments, water, and tilapia from selected sites in Winam Gulf were investigated. They were analyzed using Atomic Absorption Spectrophotometer. Fish muscles were further analyzed for omega -3 PUFAs us- ing gas chromatography. Sediment samples accumulated the highest levels of heavy metals ranging from below detection limit to as high as 277 mg/kg on dry weight basis. Zinc levels in fish muscles were the highest whereas cadmium was the lowest. Heavy metal levels in water were found to be lowest compared to sediments and fish. Omega-3 PUFAs, particu- larly alpha-linolenic, eicosapentaenoic, docosapentaenoic and docosahexaenoic acids were in substantial amounts in fish. Oil contents were in the range of (2.47- 3.87) %. There was no clear link observed between the levels of heavy metals and omega-3 PUFAs in fish although the fish muscles showed presence of these metals.

Omega-6 and omega-3 polyunsaturated fatty acid levels are reduced in whole blood of Italian patients with a recent myocardial infarction: the AGE-IM study

ObjectiveThe relationship between whole blood fatty acids and myocardial infarction (MI) risk has not been analyzed in detail, especially in Mediterranean countries. The AGE-IM (Acidi Grassi Essenziali e Infarto Miocardico) study was planned to examine the relationships between MI, whole blood fatty acids and the diet in an Italian cohort. Methods119 Patients with a recent MI and 103 control subjects were enrolled in the study. The whole blood fatty acid composition was determined; information on anthropometrics, biochemical parameters and blood pressure values were also obtained. Diet composition was assessed using a validated food frequency questionnaire from 86 cases and 72 controls. ResultsTotal PUFA, omega-6 and omega-3 PUFA (as percentage of whole blood fatty acids) were significantly lower in MI patients than in matched controls, whereas saturated and monounsaturated fatty acids were higher in cases. MI infarction risk significantly and steadily decreased with increasing levels of total PUFA (OR: 0.14) and of total omega-6 and omega-3 (OR: 0.15 and 0.37, respectively). No correlation was identified between dietary fats and MI risk or between whole blood fatty acid levels and dietary nutrients and fats. ConclusionPercentage levels of total PUFA, total omega-3 PUFA and total omega-6 PUFA are lower in MI patients than in matched control subjects in the AGE-IM cohort. These data support a favorable association not only of whole blood percentage levels of total omega-3, but also of total omega-6, with cardiovascular risk.

Polyunsaturated omega-3 fatty acids reduce lipoprotein-associated phospholipase A2 in patients with stable angina

Background and AimsIncreased consumption of omega-3 polyunsaturated fatty acids (PUFA) together with lifestyle measures and medications is recommended for the prevention of cardiovascular diseases. However, the exact mechanisms underlying observed benefits are not well defined. To this aim, we evaluated the effects of omega-3 PUFA in stable coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) on lipoprotein associated phospholipase A2 (Lp-PLA2) mass and activity and their relation to oxidized low-density lipoproteins (oxy-LDL). Methods and ResultsIn a prospective, double-blind, placebo-controlled, randomized study Lp-PLA2, oxy-LDL, myeloperoxidase and interleukin-6 were determined at baseline, 3–5 days and 30 days during administration of omega-3 PUFA 1 g/day (n = 30) or placebo (n = 24). Treatment with omega-3 PUFA resulted in reduction of Lp-PLA2 mass by 10.7%, activity by 9.3 (p = 0.026 for both) and oxy-LDL by 10.9% (p = 0.014) at 30 days, with no change in myeloperoxidase and interleukin-6. Compared with placebo, patients receiving omega-3 PUFA had lower Lp-PLA2 mass by 9.42%, activity by 9.2 (p = 0.041 for both) and oxy-LDL by 12.3% (p = 0.10) after one month, but not at 3–5 days. There were no correlations between Lp-PLA2 and both myeloperoxidase and oxy-LDL throughout the study. The multivariate model showed that only treatment with omega-3 PUFA and baseline myeloperoxidase levels were independent predictors of Lp-PLA2 mass changes at one month (R2 = 0.37, P = 0.005). ConclusionsAdministration of omega-3 PUFA can decrease Lp-PLA2 in patients with stable angina undergoing PCI. This novel effect may contribute to the benefits derived from omega-3 PUF.

Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents.

Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity and impulsivity, and is associated with long-term social, academic and mental health problems. The stimulant medications methylphenidate and amphetamine are the most frequently used treatments for ADHD, but these are not always effective and can be associated with side effects. Clinical and biochemical evidence suggests that deficiencies of polyunsaturated fatty acids (PUFA) could be related to ADHD. Children and adolescents with ADHD have been shown to have significantly lower plasma and blood concentrations of PUFA and, in particular, lower levels of omega-3 PUFA.These findings suggest that PUFA supplementation may reduce the attention and behaviour problems associated with ADHD. To compare the efficacy of PUFA to other forms of treatment or placebo in treating the symptoms of ADHD in children and adolescents. We searched the following databases in August 2011: CENTRAL (The Cochrane Library 2011, Issue 2), MEDLINE (1948 to July Week 3, 2011), EMBASE (1980 to 2011 Week 29), PsycINFO (1806 to current), CINAHL (1937 to current), BIOSIS (1969 to 30 July 2011), Science Citation Index (1970 to 30 July 2011), Social Science Citation Index (1970 to 30 July 2011), Conference Proceedings Citation Index - Science (1990 to 30 July 2011), Conference Proceedings Citation Index - Social Science and Humanities (1990 to 30 July 2011), Cochrane Database of Systematic Reviews (2011, Issue 7), DARE (2011 Issue 2), Dissertation Abstracts (via Dissertation Express) and the metaRegister of Controlled Trials (mRCT). In addition, we searched the following repositories for theses on 2 August 2011: DART, NTLTD and TROVE. We also checked reference lists of relevant studies and reviews for additional references. Two review authors independently assessed the results of the database searches. We resolved any disagreements regarding the selection of studies through consensus or, if necessary, by consultation with a third member of the review team. Two members of the review team independently extracted details of participants and setting, interventions, methodology and outcome data. If differences were identified, we resolved them by consensus or referral to a third member of the team. We made all reasonable attempts to contact the authors where further clarification or missing data were needed. We included 13 trials with 1011 participants in the review. After screening 366 references, we considered 23 relevant and obtained the full text for consideration. We excluded five papers and included 18 papers describing the 13 trials.Eight of the included trials had a parallel design: five compared an omega-3 PUFA supplement to placebo; two compared a combined omega-3 and omega-6 supplement to placebo, and one compared an omega-3 PUFA to a dietary supplement. Five of the included trials had a cross-over design: two compared combined omega-3/6 PUFA to placebo; two compared omega-6 PUFA with placebo; one compared omega-3 to omega-6 PUFA, and one compared omega-6 PUFA to dexamphetamine. Supplements were given for a period of between four and 16 weeks.There was a significantly higher likelihood of improvement in the group receiving omega-3/6 PUFA compared to placebo (two trials, 97 participants; risk ratio (RR) 2.19, 95% confidence interval (CI) 1.04 to 4.62). However, there were no statistically significant differences in parent-rated ADHD symptoms (five trials, 413 participants; standardised mean difference (SMD) -0.17, 95% CI -0.38 to 0.03); inattention (six trials, 469 participants; SMD -0.04, 95% CI -0.29 to 0.21) or hyperactivity/impulsivity (five trials, 416 participants; SMD -0.04, 95% CI -0.25 to 0.16) when all participants receiving PUFA supplements were compared to those receiving placebo.There were no statistically significant differences in teacher ratings of overall ADHD symptoms (four trials, 324 participants; SMD 0.05, 95% CI -0.18 to 0.27); inattention (three trials, 260 participants; SMD 0.26, 95% CI -0.22 to 0.74) or hyperactivity/impulsivity (three trials, 259 participants; SMD 0.10, 95% CI -0.16 to 0.35).There were also no differences between groups in behaviour, side effects or loss to follow-up.Overall, there were no other differences between groups for any other comparison. Overall, there is little evidence that PUFA supplementation provides any benefit for the symptoms of ADHD in children and adolescents. The majority of data showed no benefit of PUFA supplementation, although there were some limited data that did show an improvement with combined omega-3 and omega-6 supplementation.It is important that future research addresses current weaknesses in this area, which include small sample sizes, variability of selection criteria, variability of the type and dosage of supplementation, short follow-up times and other methodological weaknesses.

The roles of omega-3 and omega-6 fatty acids in idiopathic male infertility

The roles of omega-3 and omega-6 fatty acids in idiopathic male infertility

Dietary Omega-3 Supplementation Exacerbates Left Ventricular Dysfunction in an Ovine Model of Anthracycline-Induced Cardiotoxicity

BackgroundCumulative dose-dependent nonischemic cardiomyopathy (NICM) remains a significant risk with the use of some chemotherapeutic agents. In this context, omega-3 polyunsaturated fatty acids (PUFA) have been investigated for their cardioprotective potential in rodent and in vitro models of anthracycline toxicity, with conflicting results. This study evaluated prophylactic omega-3 PUFA supplementation in a large-animal model of anthracycline-induced NICM. Methods and ResultsMerino sheep were randomized to oral drenching with omega-3 PUFA (fish oil; n = 8) or olive oil placebo (n = 9) 3 weeks before commencing repeated intracoronary infusions of doxorubicin (DOX) to induce cardiac dysfunction. Cumulative DOX dose was 3.6 mg/kg. Drenching was continued for 12 weeks after final DOX exposure. Despite significant increases in tissue omega-3 PUFA levels (P < .05 vs placebo), omega-3–treated sheep displayed greater signs of anthracycline cardiotoxicity than placebo animals, consisting of left ventricular dilatation and a greater decline in ejection fraction (P < .05), although myocardial fibrosis burden was similar in both groups. ConclusionsDietary intake of omega-3 PUFA fails to prevent and may indeed exacerbate DOX-induced cardiotoxicity. Clinical use of omega-3 supplementation during chemotherapy should be deferred until more information is available regarding the mechanisms of interaction between fatty acids and the myocardium during anthracycline exposure.

Update on Omega-3 Polyunsaturated Fatty Acids in Early-Stage Psychotic Disorders

Polyunsaturated fatty acids (PUFAs) are the major constituents of cell membrane phospholipids. As such, they have multiple important biological roles, including in receptor binding, neurotransmission, signal transduction, and eicosanoid synthesis. A growing body of studies suggests significant reductions in PUFA levels in people with schizophrenia (Berger et al, 2006). Concordant with these findings, fatty acids, particularly the omega-3 PUFA, may have a beneficial role in the treatment of first-episode schizophrenia, and in the prevention of schizophrenia, while results in chronic schizophrenia have been mixed (Peet, 2008). We have recently tested whether supplementation with omega-3 PUFA could reduce the rate of transition to first-episode psychosis in an ultra-high risk (UHR) cohort. In our study, we randomized 81 individuals aged 13–25 years to 12 weeks of either 1.2 g/day of omega-3 PUFA or placebo, followed by a 40-week monitoring period. In all, 2 of 41 (4.9%) of those receiving the active agent transitioned to psychosis, compared with 11 of 40 (27.5%) in the placebo group, a statistically significant difference (Amminger et al, 2010). While PUFAs have been investigated in schizophrenia, their role in the onset of psychotic symptoms is unclear. Therefore, we examined the relationship between omega-3 PUFA (ie, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA)) levels in erythrocyte membrane phosphatidylethanolamine and measures of psychopathology in our UHR cohort at baseline. Erythrocyte membrane phospholipid composition closely reflects that of neuronal membranes, and provides an easily accessible indicator of brain phospholipids. While ALA, EPA, and DHA did not correlate significantly with any symptom measure, low levels of DPA and the summary score of all assessed omega-3 fatty acids (ie, ALA, EPA, DPA, and DHA) correlated with more severe negative symptoms. These correlations remained significant after adjustment for potential confounders (ie, age, sex, and nicotine use). Reduced DPA has been previously reported in neuroleptic-naive first-episode schizophrenia patients (Reddy et al, 2004). Given our intervention study provided support for the ‘dose–response' criterion (McNamara, 2011), as an increase in erythrocyte omega-3 PUFA levels reduced the rate of transition to psychosis and correlated with functional improvement, we tested if the subjects with the lowest erythrocyte omega-3 levels at baseline were at higher risk for transitioning to psychosis. To eliminate treatment effects, we only investigated those participants who had received placebo. Cox regression analyses with adjustment for age, sex, and nicotine use indicated that no single omega-3 PUFA or their summary score predicted conversion to psychosis. Following studies reporting lower levels of arachidonic acid (AA) and nervonic acid (NA), as well as DHA, in people with schizophrenia (Assies et al, 2001), we also examined if these fatty acids predicted transition to psychosis. While AA was not found to be predictive, low NA levels at baseline significantly predicted transition to psychosis (Amminger et al, submitted). As NA is a major constituent of the myelin sheath, low levels of NA could reflect suboptimal myelination in those UHR individuals who develop a psychotic disorder. The finding is consistent with the well-established finding of white matter abnormalities in schizophrenia (Ellison-Wright and Bullmore, 2009). Notably, the observation that supplementation with omega-3 PUFAs may prevent transition to psychosis suggests that omega-3 fatty acids may offset the risk conferred by decreased levels of NA. A randomized controlled multicenter phase III clinical trial of omega-3 PUFA is now underway to replicate the findings (Australian New Zealand Clinical Trials Registry - ACTRN12608000475347).

Associations of polyunsaturated fatty acids with residual depression or anxiety in older people with major depression

Depression in late life often follows a chronic course with residual depressive and anxiety symptoms. Levels of omega-3 polyunsaturated fatty acids (PUFAs) have been found to be depleted in people with major depression in the acute stage. Additionally, lower omega-3 PUFA levels have been suggested to be associated with anxiety. The aim of this study was to investigate whether PUFAs levels (omega-3 or omega-6) are correlated with residual depressive or anxiety symptoms in older people with previous depression. Participants aged 60 years or over with previous major depression in remission were enrolled from outpatient psychiatric services of four hospitals. Participants with residual depressive symptoms were defined as the Hamilton Depression Rating Scale (HDRS) scores>5, and those with anxiety were defined as sum of scores for the two anxiety subscale of HDRS≧2. The levels of fatty acids in erythrocyte membranes and in plasma were measured separately by gas chromatography. One hundred and thirty two older people with previous major depression (mean age of 68 years, range 60-86 years) were analyzed. Erythrocyte membrane linoleic acid levels had a curvilinear association with depressive symptoms and anxiety symptoms. Plasma linoleic acid levels were found to have a negative linear relationship with depressive symptoms. No significant associations were found between any omega-3 fatty acid level and depressive or anxiety symptoms. Linoleic acid levels may be a possible biomarker for residual depression and anxiety in older people with previous depression. Possible clinical applications need further investigation.

Atypical antipsychotic medications increase postprandial triglyceride and glucose levels in male rats: Relationship with stearoyl-CoA desaturase activity

Recent preclinical and clinical evidence suggests that the stearoyl-CoA desaturase-1 ( Scd1) enzyme plays a key role in the regulation of triglyceride (TG) biosynthesis and insulin sensitivity, and in vitro studies have found that antipsychotic medications up-regulate Scd1 mRNA expression. To investigate these effects in vivo, rats were treated with risperidone (1.5, 3, and 6 mg/kg/d), paliperidone (1.5, 3, and 6 mg/kg/d), olanzapine (2.5, 5, and 10 mg/kg/d), quetiapine (5, 10, and 20 mg/kg/d), haloperidol (1, and 3 mg/kg/d) or vehicle through their drinking water for 40 days. Effects on liver Scd1 mRNA expression and an index of Scd1 activity (the plasma 18:1/18:0 ratio, ‘desaturation index’) were determined, as were postprandial plasma triglyceride (TG), glucose, insulin, and polyunsaturated fatty acid (PUFA) levels. All atypical antipsychotics increased the plasma 18:1/18:0 ratio, but not liver Scd1 mRNA expression, at doses found to also increase plasma TG levels. Among all rats (n = 122), the plasma 18:1/18:0 ratio accounted for 56% of the variance in TG concentrations. The plasma 18:1/18:0 ratio was also positively associated with erythrocyte and heart membrane phospholipid 18:1 n-9 composition. All antipsychotics except risperidone increased glucose levels at specific doses, and none of the antipsychotics significantly altered insulin levels. The plasma 18:1/18:0 ratio accounted for 20% of the variance in glucose levels. Plasma omega-3 and omega-6 PUFA levels were inversely correlated with the plasma 18:1/18:0 ratio and TG and glucose levels. These in vivo data demonstrate that different atypical antipsychotic medications increase the plasma 18:1/18:0 ratio in association with elevations in postprandial TG and glucose levels, and that concomitant elevations in PUFA biosynthesis oppose these effects.

Associations of Plasma Phospholipid Omega-6 and Omega-3 Polyunsaturated Fatty Acid Levels and MRI Measures of Cardiovascular Structure and Function: The Multiethnic Study of Atherosclerosis

Background. The association between plasma omega-6 fatty acids and cardiovascular disease (CVD) is unclear, and discrepancy remains concerning the cardiovascular benefit of the omega-3 fatty acid alpha-linolenic acid. Methods. Associations of plasma phospholipid fatty acid levels (arachidonic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid (DHA), and alpha-linolenic acid) with cardiac magnetic resonance imaging measures of left ventricular (LV) mass, LV volume, ejection fraction, stroke volume, and aortic distensibility were investigated in 1,274 adults. Results. Results of multivariate analysis showed no statistically significant associations of plasma omega-6 or omega-3 levels with cardiac magnetic resonance imaging measures. Stratification by gender revealed a positive association between DHA and LV mass in women (β = 1.89, P = 0.02; P interaction = 0.003) and a trend for a positive association between DHA and ejection fraction in men (β = 0.009, P = 0.05; P interaction = 0.03). Conclusion. Additional research is warranted to clarify the effects of plasma DHA on cardiac structure and function in women versus men.

Increased breath ethane levels in medicated patients with schizophrenia and bipolar disorder are unrelated to erythrocyte omega-3 fatty acid abundance

Oxidative stress has been reported to be elevated in mental illness. Preliminary evidence suggests this phenomenon can be assessed non-invasively by determining breath levels of the omega-3 polyunsaturated fatty acid (PUFA) oxidation product ethane. This study compares alkane levels in chronic, medicated, patients with schizophrenia or bipolar disorder with those in healthy controls. Both ethane and butane levels were significantly increased in patients with schizophrenia or bipolar disorder, although elevated butane levels were likely due to increased ambient gas concentrations. Ethane levels were not correlated with symptom severity or with erythrocyte omega-3 PUFA levels. Our results support the hypothesis that oxidative stress is elevated in patients with schizophrenia and bipolar disorder leading to increased breath ethane abundance. This does not appear to be caused by increased abundance of omega-3 PUFA, but rather is likely due to enhanced oxidative damage of these lipids. As such, breath hydrocarbon analysis may represent a simple, non-invasive means to monitor the metabolic processes occurring in these disorders.