Low Omega-3 Polyunsaturated Fatty Acid Research Articles

Low omega-3 polyunsaturated fatty acid status predicts reduced response to standard antidepressants in patients with major depressive disorder

The mammary epithelium undergoes several rounds of extensive proliferation during the female reproductive cycle. Its expansion is a tightly regulated process, fueled by the mammary stem cells and these cells' unique property of self-renewal. Sufficient new cells have to be produced to maintain the integrity of a tissue, but excessive proliferation resulting in tumorigenesis needs to be prevented. Three well-known tumor suppressors, p53, p16INK4a, and p19ARF, have been connected to the limiting of stem cell self-renewal and proliferation. Here we investigate the roles of these three proteins in the regulation of self-renewal and proliferation of mammary epithelial cells. Using mammary epithelial-specific mouse models targeting Trp53 and Cdkn2a, the gene coding for p16INK4a and p19ARF, we demonstrate that p53, p16INK4a, and p19ARF do not play a significant role in the limitation of normal mammary epithelium self-renewal and proliferation, whereas in the presence of the inflammatory cytokine TNF-α, Trp53−/− Cdkn2a−/− mammary basal cells exhibit amplified proliferation.

Bidirectional longitudinal associations of omega-3 polyunsaturated fatty acid plasma levels with depressive disorders

BackgroundTemporality of the association of low omega-3 polyunsaturated fatty acid (n-3 PUFA) plasma levels with depression remains questionable. To determine the underlying nature of these associations, this study examined the bidirectional longitudinal associations of n-3 PUFA plasma levels with (presence, onset and course of) depressive disorders and symptoms. MethodsBaseline (n = 2912, 28.6% with current depressive disorder) and 6-year follow-up data (n = 1966, 13.0% with current depressive disorder) of the Netherlands Study of Depression and Anxiety (NESDA) were used. Depression diagnoses and symptoms were based on psychiatric interviews and self-report questionnaires. N-3 PUFA levels (ratio of total fatty acids (mmol%)), were assessed using nuclear magnetic resonance. ResultsUsing two waves of data, n-3 PUFA levels were lower among depressed persons, as compared to healthy controls (Beta = −0.047, SE = 0.011, p < .001). Nevertheless, baseline n-3 PUFA levels were not consistently associated with subsequent change in depressive symptoms, onset or remission of depressive disorders over 6 years. Furthermore, the difference in n-3 PUFA levels detected at baseline between depressed and non-depressed participants tended to dissipate over 6 years (depression-by-time estimate: p = .011). Finally, subjects depressed both at baseline and at 6-year follow up had consistently lower n-3 PUFA levels over the entire follow-up as compared to those who had never been depressed. Change in depressive disorders across waves was not consistently accompanied by change in n-3 PUFA levels over time. LimitationsNo data on intermediate time points and EPA levels were available. ConclusionsDespite significant cross-sectional associations between n-3 PUFA plasma levels and depressive disorders and severity, this 6-year longitudinal study could not confirm an uni- or bidirectional association over time. The association between depression and n-3 PUFA plasma levels is unlikely to be causal.

Omega-3 polyunsaturated fatty acids status and cognitive function in young women

BackgroundResearch indicates that low omega-3 polyunsaturated fatty acid (n-3 PUFA) may be associated with decreased cognitive function. This study examined the association between n-3 PUFA status and cognitive function in young Australian women.MethodsThis was a secondary outcome analysis of a cross-sectional study that recruited 300 healthy women (18–35 y) of normal weight (NW: BMI 18.5–24.9 kg/m2) or obese weight (OB: BMI ≥30.0 kg/m2). Participants completed a computer-based cognition testing battery (IntegNeuro™) evaluating the domains of impulsivity, attention, information processing, memory and executive function. The Omega-3 Index (O3I) was used to determine n-3 PUFA status (percentage of EPA (20:5n-3) plus DHA (22:6n3) in the red cell membrane) and the participants were divided into O3I tertile groups: T1 < 5.47%, T2 = 5.47–6.75%, T3 > 6.75%. Potential confounding factors of BMI, inflammatory status (C-reactive Protein), physical activity (total MET-min/wk), alpha1-acid glycoprotein, serum ferritin and hemoglobin, were assessed. Data reported as z-scores (mean ± SD), analyses via ANOVA and ANCOVA.ResultsTwo hundred ninety-nine women (26.9 ± 5.4 y) completed the study (O3I data, n = 288). The ANOVA showed no overall group differences but a significant group × cognition domain interaction (p < 0.01). Post hoc tests showed that participants in the low O3I tertile group scored significantly lower on attention than the middle group (p = 0.01; ES = 0.45 [0.15–0.74]), while the difference with the high group was borderline significant (p = 0.052; ES = 0.38 [0.09–0.68]). After confounder adjustments, the low group had lower attention scores than both the middle (p = 0.01) and high (p = 0.048) groups. These findings were supported by univariate analyses which found significant group differences for the attention domain only (p = 0.004).ConclusionsCognitive function in the attention domain was lower in women with lower O3I, but still within normal range. This reduced but normal level of cognition potentially provides a lower baseline from which cognition would decline with age. Further investigation of individuals with low n-3 PUFA status is warranted.

Lipid correlates of antidepressant response to omega-3 polyunsaturated fatty acid supplementation: A pilot study

Low omega-3 polyunsaturated fatty acid (PUFA) levels are seen in major depression. We examined effects of six weeks of fish oil supplementation on clinical characteristics in 16 patients with symptomatic major depressive disorder, and tested plasma phospholipid levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as correlates of clinical response. Depression symptoms improved after supplementation (p=0.007). The reduction in depression severity was not predicted by baseline PUFA levels but did exhibit a relationship with endpoint PUFAs, correlating negatively with DHA as a percentage of plasma phospholipids (DHA%; R2=0.60, p=0.004), adjusting for endpoint EPA%; and correlating positively with endpoint EPA% (R2=0.58, p=0.007), adjusting for endpoint DHA%. Thus, the higher the proportion of DHA to EPA, the greater the reduction in depression severity (r=−0.43, p=0.097). Five patients showed a decrease of >50% on the 17-item Hamilton Depression Rating Scale and a final score <7 and were thus not only responders but met standard criteria for remission, and were distinguished from non-responders by higher levels of DHA% (p=0.03). This pilot study suggests that post-supplementation DHA% levels may be a necessary target for antidepressant response to fish oil, and that this may depend to some extent on the efficacy of EPA conversion to DHA.

Comparison of proximate and fatty acid compositions of wild brown trout and farmed rainbow trout

The purpose of this study was to compare the fatty acid and proximate composition of two commercially exploited trout species (wild brown trout (WBT) and farmed rainbow trout (FRT)). The mean crude lipid content in FRT (4.3%) was significantly higher than that in WBT (2.7%). Total saturated fatty acid concentration (27.7%) in WBT was significantly higher than that in FRT (21.4%). However, monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) concentrations in FRT were significantly greater than those of WBT. While the omega-6 PUFA concentration of WBT was fairly low, total omega-3 PUFA concentration was significantly higher compared with omega-6 PUFA. In contrast to WBT, the FRT contained high omega-6 and low omega-3 PUFA concentrations. Linolenic, docosahexaenoic (DHA), eicosapentaenoic (EPA) acids and C20:3n-3 components of omega-3 PUFAs were higher and significantly different between the two species. The ratio of omega-3 to omega-6 fatty acids in WBT was significantly higher compared to FRT. The results indicated that muscle lipids of both species are rich in EPA + DHA, thus beneficial in human nutrition.Keywords: SFA, MUFA, PUFA, Salmo trutta macrostigma, Oncorhynchus mykiss, EPA, DHA

Enhancement of activity and selectivity of Candida rugosa lipase and Candida antarctica lipase A by bioimprinting and/or immobilization for application in the selective ethanolysis of fish oil

Candida rugosa lipase (CRL) and Candida antarctica lipase A (CALA) with improved activity and selectivity were prepared for use in organic solvent media. CRL bioimprinted with fatty acids exhibited eightfold enhanced transesterification activity in hexane. Combination of bioimprinting and coating with lecithin or with immobilization did not improve the activity further. CALA was immobilized with and without bioimprinting, none of which improved the activity. All modified lipases were tested for selective ethanolysis of fish oil to concentrate omega-3 polyunsaturated fatty acids (PUFA). None of the preparations, except the immobilized ones catalysed ethanolysis. Immobilized CRL-catalyzed ethanolysis giving 27% (v/v) ethyl esters (EE) in 48 h, of which 43 mol% was oleic acid but no PUFA was detected in the EE fraction. Fatty acid selectivity of CALA was significantly improved by immobilization combined with bioimprinting, resulting in 5.5-fold lower omega-3 PUFA in EE.

Aggressive dogs are characterized by low omega-3 polyunsaturated fatty acid status

Canine aggressive behaviour is one of the most common problems being reported by dog owners. However, the biochemical basis of this phenomenon remains unclear. In humans, alterations in omega-3 plasma polyunsatured fatty acids and elevated omega6/omega-3 ratio have been linked to behavioural alterations, including aggression. Thus far, however, the relationship between plasma polyunsatured fatty acid status and aggression has not been investigated in the dog. In the present study we sought to investigate whether polyunsatured fatty acid status could be altered in plasma of pathologically aggressive Canis familiaris. Eighteen adult male German Shepherd dogs, aged 4.9 +/- 0.9 years, showing no clinical signs but aggression, were investigated. Eighteen healthy male dogs, aged 4.8 +/- 0.7 years, with a negative history of behavioural and neurological disorders served as controls. Baseline fasting plasma polyunsatured fatty acid composition was determined by gas chromatography. Compared to normal dogs, aggressive dogs showed lower docosahexaenoic acid (22:6 n-3) concentrations and a higher omega6/omega-3 ratio. In addition, they showed reduced cholesterol and bilirubin concentrations compared to their normally behaving counterparts. Altogether, our results suggest that low omega-3 fatty acids may adversely impact behaviour in dogs, resulting in greater propensity to aggression. However, given the cross-sectional design of our study, we cannot claim any causal relationship between the presence of alterations in fatty acid status and canine aggressiveness. Whether omega-3 fatty acids supplementation may be useful to reduce aggressive behaviour in the dog deserves further investigation.

ω−3 Fatty acid deficiency in major depressive disorder is caused by the interaction between diet and a genetically determined abnormality in phospholipid metabolism

Omega-3 fatty acids are a type of polyunsaturated fatty acid (PUFA). A growing body of evidence suggests that this form PUFA is a useful and well tolerated treatment for major depressive disorder, a common and serious mental illness. The efficacy of omega-3 PUFA is routinely explained as being due to a deficiency caused by inadequate dietary intake of this class of fatty acid. The hypothesis considered states that low omega-3 PUFA abundance in patients with major depressive and related disorders is due to an underlying genetically determined abnormality. The hypothesis can explain why although a specific and consistent deficit in omega-3, but not omega-6, PUFA occurs in major depressive and related disorders, the literature does not consistently support the notion that this is due to deficient dietary intake. Specifically it is hypothesized that having genetically determined low activity of fatty acid CoA ligase 4 and/or Type IV phospholipase A(2) combined with the low dietary availability of omega-3 PUFA results in reduced cellular uptake of omega-3 PUFA and constitutes a risk factor for depression. The hypothesis also has important consequences for the pharmacological treatment of depression in that it predicts that administering agents which enhance phospholipid synthesis, particularly those containing ethanolamine such as CDP-ethanolamine, should be effective antidepressants especially when co-administered with omega-3 PUFA.