ArticleLiterature Review

Omega3 Fatty Acids: Evidence Basis for Treatment and Future Research in Psychiatry

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Abstract

To determine if the available data support the use of omega-3 essential fatty acids (EFA) for clinical use in the prevention and/or treatment of psychiatric disorders. The authors of this article were invited participants in the Omega-3 Fatty Acids Subcommittee, assembled by the Committee on Research on Psychiatric Treatments of the American Psychiatric Association (APA). Published literature and data presented at scientific meetings were reviewed. Specific disorders reviewed included major depressive disorder, bipolar disorder, schizophrenia, dementia, borderline personality disorder and impulsivity, and attention-deficit/hyperactivity disorder. Meta-analyses were conducted in major depressive and bipolar disorders and schizophrenia, as sufficient data were available to conduct such analyses in these areas of interest. The subcommittee prepared the manuscript, which was reviewed and approved by the following APA committees: the Committee on Research on Psychiatric Treatments, the Council on Research, and the Joint Reference Committee. The preponderance of epidemiologic and tissue compositional studies supports a protective effect of omega-3 EFA intake, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mood disorders. Meta-analyses of randomized controlled trials demonstrate a statistically significant benefit in unipolar and bipolar depression (p = .02). The results were highly heterogeneous, indicating that it is important to examine the characteristics of each individual study to note the differences in design and execution. There is less evidence of benefit in schizophrenia. EPA and DHA appear to have negligible risks and some potential benefit in major depressive disorder and bipolar disorder, but results remain inconclusive in most areas of interest in psychiatry. Treatment recommendations and directions for future research are described. Health benefits of omega-3 EFA may be especially important in patients with psychiatric disorders, due to high prevalence rates of smoking and obesity and the metabolic side effects of some psychotropic medications.

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... Omega-3 fatty acids may also inhibit secretion of inflammatory cytokines, dampening adrenal corticosteroid hormone release and its related mood-altering effects (72,74). 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 Efficacy Approximately 15 to 20 randomized, placebo-controlled trials and a few open studies with EPA and/or DHA suggest that omega-3 supplementation at doses about five or more times the current U.S. dietary intake may yield antidepressant and/or mood-stabilizing effects, particularly as adjunctive therapy (75). ...
... A number of meta-analyses of omega-3 RCTs for depression (75)(76)(77)(78) suggest efficacy over placebo, but are limited by several factors, such as the combination of augmentation and monotherapy trials and the inclusion of bipolar samples in some cases. Most of the trials reviewed are small, with a wide range of omega-3 preparations and doses (1-10 g/day). ...
... Regarding DHA, which is relatively understudied compared with EPA, one RCT with 36 subjects showed lack of efficacy of 2-g/day DHA monotherapy for depression (83). A more recent three-armed pilot dose-finding study of DHA monotherapy (84) found a response pattern similar to Peet and Horrobin's results for EPA (75), Q6 with the greatest efficacy for DHA doses of 1 g/day compared with 2 and 4 g/day (84), which also suggests possible overcorrection in the patients from Marangell et al. (83). ...
... The first is via stress reduction. Omega-3 PUFAs modulate a wide range of neural substrates that contribute to emotional regulation, such as noradrenaline, dopamine, serotonin, and endocannabinoid systems (Freeman et al., 2006;Lafourcade et al., 2011). In addition, omega-3 PUFAs reduce stressor-evoked augmentation of autonomic activity (Ginty & Conklin, 2012;Hamazaki et al., 2005;Matsumura et al., 2017) as a whole-body preparation for fight-or-flight stress responses. ...
... The second pathway is via a reduction in depression. Omega-3 PUFAs are known to exert antidepressant effects (Freeman et al., 2006;Lin & Su, 2007), including in mothers with postpartum depression (Urech et al., 2020;Zhang et al., 2020). Because postpartum depression is a risk factor for infant maltreatment (Stith et al., 2009), intake of omega-3 PUFAs may reduce infant maltreatment via a reduction in postpartum depression. ...
Article
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Background Intake of omega-3 polyunsaturated fatty acids (PUFAs) has favorable effects, including reducing violent and aggressive behaviors, but its association with infant maltreatment is unknown. We therefore tested the hypothesis that maternal intake of omega-3 PUFAs is associated with a lower risk of infant maltreatment. Methods Participants were 92 191 mothers involved in the ongoing Japan Environment and Children's Study. Omega-3 PUFA intake during pregnancy was measured using a food frequency questionnaire. Infant maltreatment was assessed using a self-reported questionnaire administered at 1 and 6 months postpartum. Results Analysis using the lowest quintile of intake as a reference revealed that the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for cases of ‘hitting’ decreased as quintiles increased, with values for the second to fifth quintiles of 0.93 (95% CI 0.77–1.13), 0.79 (95% CI 0.64–0.97), 0.78 (95% CI 0.64–0.96), and 0.72 (95% CI 0.59–0.89), respectively. Adjusted ORs (95% CIs) for ‘shaking very hard’ at 6 months were 0.87 (0.73–1.04), 0.81 (0.67–0.97), 0.73 (0.61–0.89), and 0.78 (0.65–0.94), respectively. Adjusted ORs for ‘leaving alone at home’ for the second to fifth quintiles were 0.92 (0.87–0.98), 0.91 (0.86–0.97), 0.94 (0.88–0.99), and 0.85 (0.80–0.90), respectively. Conclusions Higher maternal intake of omega-3 PUFAs during pregnancy was associated with fewer cases of hitting and violent shaking and leaving the child alone at home, implying a lower risk of infant maltreatment. Our results indicate the potential applicability of omega-3 PUFAs in reducing infant maltreatment.
... The Mediterranean diet is associated with a lower risk of depression (120) . Eicosapentaenoic acid and docosahexaenoic acid are effective in treating mood disorders, impulse control disorders, and psychotic disorders (121) . Both aerobic and resistance exercise are beneficial for depression, and the higher the intensity and volume of exercise, the more effective (123), (124) . ...
... Mediterranean diet is associated with a lower risk of depression (120) . The American Psychiatric Association recommends supplementation of eicosapentaenoic acid and docosahexaenoic acid among n-3 (omega-3) unsaturated fatty acids for mood disorders, impulse control disorders, and psychotic disorders (121) . ...
Article
Nutritional disorders diminish the effectiveness of physical therapy. The pathogenesis of nutritional disorders, such as sarcopenia, frailty, and cachexia, differs from disease to disease. Disease-specific nutrition can maximize the function, activity, participation, and quality of life for patients undergoing physical therapy, a practice known as nutritional physical therapy. Understanding and practicing disease-specific nutritional physical therapy is essential to meet patients' diverse needs and goals with any disease. Thus, the physical therapist division of the Japanese Association of Rehabilitation Nutrition, with advice from the Japanese Society of Nutrition and Swallowing Physical Therapy, developed this review. It discusses the impact of disease-specific nutritional physical therapy on sarcopenia and frailty in community-dwelling older adults, obesity and metabolic syndrome, critical illness, musculoskeletal diseases, stroke, respiratory diseases, cardiovascular diseases, diabetes, renal disease, cancer, and sports.
... In spite of the large variability in the design of experiments to evaluate the action of different dietary elements on cognitive abilities, there is a consensus that a deficiency of omega-3 fatty acids in rodents results in impaired learning and memory. Dietary deficiency of omega-3 fatty acids in humans has been associated with an increased risk of several mental disorders, including attention-deficit disorder, dyslexia, dementia, depression, bipolar disorder and schizophrenia [69]. ...
Article
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Proper nutrition is a key factor in physical performance, but there are also indications of an impact of dietary components on the brain function. Therefore, the aim of the study was to assess the impact of macronutrients and water on cognitive performance. Assumptions of the Mediterranean diet correlate with better global cognition, episodic memory, lower risk of cognitive impairment and neurodegenerative diseases. In turn, a high-fat and high-sugar diet shows the opposite effect. Omega-3 fatty acids could be used as a preventive tool for cognitive decline, but there is still insufficient evidence if supplementation improves cognitive functions. The proper intake of protein may be important in cognitive performance. Tyrosine seems to be potentially effective in inhibition of fatigue under extreme conditions, and the influence of BCAA on cognitive performance is still unclear. An appropriate glucose level is a critical factor for brain functions. Carbohydrate supplementation before and during exercise is associated with enhanced brain activation and decreased exercise perception, as well as improved cognitive functions. Dehydration worsens cognitive performance, especially for tasks requiring attention, executive functions and coordination. Based on the review of available studies, it should be assumed that proper nutrition might play a relevant role in athletes' cognitive performance.
... DHA in combination with EPA provides the best results for preventing atherosclerosis, Alzheimer's, rheumatoid arthritis, dementia, and other diseases [4]. Recently published studies have emphasized the importance of utilization of very-long-chain (LC) ω-3 FAs as they play a key role in sharpening learning abilities at childhood and their behavior [5] and also decreased the burden of psychiatric sickness in young age adults [6]. e daily recommended consumption of EPA and DHA ranged from 250 mg to 1000 mg for normal adults and preferably higher intake requirements are suggested for both pregnant and lactating females [7]. ...
Article
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In the present study, fish oil (FO) and wall material were supplemented to milk to produce spray-dried powder (SDP). Furthermore, the mandate of the study was to enlighten the effect of spray-drying (SD) operating conditions on functional and oxidative quality of produced SDP samples. Purposefully, the cow milk was supplemented with 3% FO as omega-enriched source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for development of milk and FO blends (MFOBs). The lecithin was used as an emulsifier and maltodextrin was supplemented as the wall material (WM) in the MFOBs. Initially, the FO, milk fat (MF), and MFOB samples were characterized for EPA, DHA, and peroxide value (PV) before the SD. The SD of MFOB samples was carried out to produce SDP samples by using a mini spray dryer. Central composite design (CCD) with face-centered rotation was used to optimize SD independent conditions such as inlet air temperature (IAT), pump speed (PS), maltodextrin percentage (MD), and needle speed (NS) in the ranges of 160–200°C, 3–9 mL/min, 10–30%, and 5–9 s, respectively. The encapsulation efficiency (EE) ranged between 89.30 and 81.57%. The EPA and DHA retentions were in the ranges of 2.19–1.87 g/100 g and 3.20–2.75 g/100 g, respectively. The highest results for responses were observed on the following conditions: IAT was 160°C, PS was 9 mL/min, MD was 30%, and NS was 9 s, respectively; the minimum values of response factors were obtained on the following conditions: IAT was 200°C, PS was 3 mL/min, MD was 10%, and NS was 5 s, respectively. The percent losses of EPA and DHA were noted in the range of 2–18%. The IAT was observed as main factor for FA reduction in SDP samples. The SDP samples were stable, and low rate of peroxide values was noted. Overall, spray drying can be potentially used to incorporate the essential fatty acids in milk to produce stable SDP for food applications.
... blood pressure, platelet reactivity, thrombosis, cardiac arrhythmia and the risk of sudden cardiac death, heart rate variability, and inflammation [33][34][35][36]. Further, EPA and DHA have a protective effect in mood disorders [37] and can reduce symptoms in patients with depression [38][39][40][41]. Brain function is also affected by DHA; low levels of DHA has been found in the brains of persons suffering from Alzheimer's disease, and it has been demonstrated that the risk of brain injury can be decreased, and its treatment benefited by DHA [30,42,43]. ...
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Plukenetia volubilis is an underutilized oilseed crop native to the Amazon basin, where it has been utilised by humans since Incan times. The large seeds contain approx. 45–50 % lipid, of which approx. 35.2–50.8 % is α-linolenic acid (C18:3 n-3, ω-3) and approx. 33.4–41.0 % is linoleic acid (C18:2 n-6, ω-6), the two essential fatty acids required by humans. The seeds also contain 22–30 % protein and have antioxidant properties. Due to its excellent nutritional composition and good agronomic properties, it has attracted increasing attention in recent years, and cultivation is expanding. When considering current global challenges, a reformation of our food systems is imperative in order to ensure food security, mitigation of climate change, and alleviation of malnutrition. For this purpose, underutilized crops may be essential tools, which can provide agricultural hardiness and reduced need for external inputs, climate resilience, diet diversification, and improved income opportunities for smallholders. Plukenetia volubilis is a promising up and coming crop in this regard and has considerable potential for further domestication; it has an exceptional oil composition, good sensory acceptability, is well suited for cultivation, and has numerous potential applications in, e.g. gastronomy, medicine, and cosmetics.
... The MedD supplies ALA through seeds and nuts, and encourages consumption of seafood [82]. Indeed, low dietary intake of foods supplying LCPUFA has been associated with DD [83,84]. ...
Article
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Background: The importance of foods or food constituents in mental health is increasingly recognized, and “nutritional psychiatry” is a growing discipline. Objective: This narrative review aims to present work supporting associations between food or food constituents and mental health, specifically depressive disorders. Methods: The data presented is derived from preclinical and clinical work, including in vitro and in vivo assays, as well as observational studies and randomized clinical trials of dietary interventions. The focus of the review is the mediation of inflammatory processes and oxidative stress by dietary constituents that are an integral part of a healthy diet, such as the Mediterranean diet and similar. Results and Discussion: We present evidence for the role of the diet in prevention and management of depressive disorders, beyond the effect of individual nutrients. The findings indicate that among the dietary components with higher degree of evidence to influence depressive disorders are long chain n-3 polyunsaturated fatty acids (EPA and DHA), and various dietary bioactive compounds, especially plant-derived secondary metabolites represented by polyphenols such as flavonoids and resveratrol. Conclusion: Diet exerts an important role on mental health, and evidence indicates that some dietary constituents contribute to the prevention of depressive disorders.
... The Academy of Nutrition and Dietetics recommends that the general population consume 500 mg/day of EPA and DHA [42], but data from a nationally representative sample revealed that the median intake from food and dietary supplements was 18 and 15 mg/day, respectively [43]. For those with preexisting conditions (e.g., mood disorders, cardiovascular disease), the recommendations are even higher [44,45]. Although it can be Fig. 4 Omega-3 supplementation lowered overall IL-6 release throughout an acute stressor (p = 0.03). ...
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Higher levels of omega-3 track with longer telomeres, lower inflammation, and blunted sympathetic and cardiovascular stress reactivity. Whether omega-3 supplementation alters the stress responsivity of telomerase, cortisol, and inflammation is unknown. This randomized, controlled trial examined the impact of omega-3 supplementation on cellular aging-related biomarkers following a laboratory speech stressor. In total, 138 sedentary, overweight, middle-aged participants (n = 93 women, n = 45 men) received either 2.5 g/d of omega-3, 1.25 g/d of omega-3, or a placebo for 4 months. Before and after the trial, participants underwent the Trier Social Stress Test. Saliva and blood samples were collected once before and repeatedly after the stressor to measure salivary cortisol, telomerase in peripheral blood lymphocytes, and serum anti-inflammatory (interleukin-10; IL-10) and pro-inflammatory (interleukin-6; IL-6, interleukin-12, tumor necrosis factor-alpha) cytokines. Adjusting for pre-supplementation reactivity, age, sagittal abdominal diameter, and sex, omega-3 supplementation altered telomerase (p = 0.05) and IL-10 (p = 0.05) stress reactivity; both supplementation groups were protected from the placebo group’s 24% and 26% post-stress declines in the geometric means of telomerase and IL-10, respectively. Omega-3 also reduced overall cortisol (p = 0.03) and IL-6 (p = 0.03) throughout the stressor; the 2.5 g/d group had 19% and 33% lower overall cortisol levels and IL-6 geometric mean levels, respectively, compared to the placebo group. By lowering overall inflammation and cortisol levels during stress and boosting repair mechanisms during recovery, omega-3 may slow accelerated aging and reduce depression risk. ClinicalTrials.gov identifier: NCT00385723.
... Omega-3 fatty acids appear to have a role in preventing the onset of psychosis in high risk individuals (44,45). The results of meta-analyses, however, failed to provide firm evidence of the efficacy of omega-3 fatty acids in the treatment of schizophrenia (46)(47)(48)(49). They confirmed, however, the benefits of omega-3 fatty acids for the treatment of depression symptoms, especially when given at high doses in combination with antidepressants (50,51) Studies of the treatment of bipolar disorders showed that mega-3 fatty acid supplementation was effective in reducing depressive symptoms, but had no effects on the symptoms of mania (52,53). ...
Article
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Modern approaches to management of medical conditions are based on a holistic view, taking into account bidirectional connections between physical and mental health. The current pharmacologically focused model has so far provided modest benefits in addressing the burden of poor mental health. Convincing data suggest that diet quality and select nutrient-based supplements might influence a range of neurochemical modulatory activities, improving the management of mental disorders. Examples of these nutrient-based supplements include omega-3 fatty acids, S-adenosyl methionine, N-acetyl cysteine, zinc, B vitamins (including folic acid), and vitamin D. The traditional Mediterranean diet is considered to be the most beneficial diet in our region. Based on the results of preclinical studies, we are increasingly aware of the role of intestinal microbiota in the pathogenesis and potential treatment of mental disorders. Bidirectional signalling between the brain and the gut microbiome involving vagal neurocrine and endocrine signalling mechanisms influences mental and physical wellbeing. These findings suggest that using prebiotics, probiotics or in the strict sense psychobiotics, as well as incorporating fermented foods in the diet, could have a potential role in the management of mental disorders. As of now, we lack sufficient evidence to implement recommendations for dietary supplements in treatment guidelines, however, this might change in light of emerging data from contemporary research studies, at least for certain indications. Citirajte kot/Cite as: Plemenitaš a. [Nutrition and dietary supplements in psychiatric diseases]. Zdrav Vestn. 2018;87(1-2):81-90.
... On the other hand, an adequate intake of omega-3 fatty acids, and in particular docosahexaenoic acid, DHA, seems to improve cognitive abilities in the elderly [38,42,45], including positive results in patients with mood disorders [46]. Studies on the role of DHA in modulating cognitive properties have also identified its importance in the development of the nervous system of children [47,48]. ...
Article
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Although diet has contributed significantly to the evolution of human beings, the composition of the diet that has most affected this phenomenon is still an open issue. Diet has undoubtedly participated in the acquisition of the skills that underlie the differentiation of humans from other animal species and in this context the development of the nervous system has played a primary role. This paper aimed to: (1) outline the relationship between diet and human evolution; (2) evaluate how a variation in food consumption may have contributed to the enhancement of cognitive and adaptive capacities. The most widespread diet among the ancient populations that showed the highest levels of civilization (that is well-organized societies, using advanced technical tools, and promoting art and science) was very close to what is now defined as the Mediterranean diet. This suggests that a dietary approach typical of the Mediterranean basin (little meat and some fish; abundant cereals, legumes, fruit, vegetables and wine) significantly increased the intake of antioxidant molecules, including polyphenols, which along with other factors may have modulated the cognitive evolution of humans.
... Researchers recommend a daily dose of 1.5 to 2.5 g of combined long-chain omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Lakhan and Vieira, 2008;Lim et al., 2016). The American Psychiatry Association guidelines also support increasing omega-3 intake for people suffering from mental disorders by consuming at least 1 g of EPA + DHA daily, which is also inline with the guidelines of the American Heart Association (Freeman et al., 2006). There is also evidence that more than 3.0 g per day of omega-3 is not any more effective in treating affective disorders (Grubb, 1990). ...
Article
Approximately 30% of patients with major depressive disorder (MDD) present resistance to current pharmacological therapies. There is the possibility that an appropriate nutritional regimen can maintain euthymia. Poor dietary pattern and lack of nutritional knowledge are common among today's population; nutrient-rich foods are being replaced by highly processed foods that lead to a higher risk of developing chronic diseases such as metabolic syndrome, hypercholesterolemia, and diabetes. There is growing evidence of the beneficial role of vitamins and dietary supplements for improving symptoms in a range of affective disorders by regulating the gut microbiome, gut-brain axis, and neurotransmitter levels. Reduced GABA neurotransmission is regularly observed in MDD. Moreover, positive allosteric GABA modulators (i.e benzodiazepines) are widely prescribed to alleviate depression symptoms, but their use needs to be limited, as it can lead to addiction. An alternative option may be the adherence to a ketogenic diet, which consists of low-carbohydrate, moderate-protein, and high-fat intake. It is mainly known for its beneficial role in weight-loss, refractory epilepsy treatment, and balancing glucose levels. A ketogenic diet can also increase GABA levels to aid the mechanism of action of monoaminergic drugs. Thus, it could potentially be used in the treatment for affective disorders due to its potential role in GABA/glutamate balance. While more research is needed before this regimen can be regularly recommended to patients, here we discuss evidence that may encourage physicians to prescribe ketogenic diet as an adjuvant for patients receiving psychotherapy and pharmacology.
... For this reason, its intake through the consumption of fish has been fundamental for encephalization during the human evolution [32]. Furthermore, n-3 PUFAs deficiency leads to impaired learning and memory in rodents [33,34], while it increases the risk of several mental disorders in humans, such as dementia, depression, bipolar disorder and schizophrenia [35][36][37]. ...
Article
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The functioning of our brain depends on both genes and their interactions with environmental factors. The close link between genetics and environmental factors produces structural and functional cerebral changes early on in life. Understanding the weight of environmental factors in modulating neuroplasticity phenomena and cognitive functioning is relevant for potential interventions. Among these, nutrition plays a key role. In fact, the link between gut and brain (the gut-brain axis) is very close and begins in utero, since the Central Nervous System (CNS) and the Enteric Nervous System (ENS) originate from the same germ layer during the embryogenesis. Here, we investigate the epigenetic mechanisms induced by some nutrients on the cognitive functioning, which affect the cellular and molecular processes governing our cognitive functions. Furthermore, epigenetic phenomena can be positively affected by specific healthy nutrients from diet, with the possibility of preventing or modulating cognitive impairments. Specifically, we described the effects of several nutrients on diet-dependent epigenetic processes, in particular DNA methylation and histones post-translational modifications, and their potential role as therapeutic target, to describe how some forms of cognitive decline could be prevented or modulated from the early stages of life. © 2021. the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0).
... Sufficient DHA and EPA consumption during pregnancy is an important factor for optimum brain growth and development in fetuses and infancy, which has beneficial effects on the learning and memory of children (Weichselbaum et al., 2015). Several studies have suggested that the consumption of ω-3 fatty acids was associated with the reduction in risk and severity of depressive disorders and other mental health related disorders such as bipolar disorder, anxiety, etc. (Stoll et al., 1999;Su et al., 2003;Freeman et al., 2006). ...
... • Insufficient evidence for therapeutic efficacy of omega-3 PUFAs [125][126][127][128]. ...
Article
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While the role of omega-3 polyunsaturated fatty acids (PUFAs) in physical health is well established, it is becoming increasingly evident that they are also important for mental health. A decrease in the intake of omega-3 PUFAs in Western countries over recent decades may have affected the prevalence of mental disorders. Omega-3 PUFAs play fundamental roles in the development, functioning and aging of the brain. In humans, dietary deficiencies of omega-3 PUFAs, such as docosahexaenoic acid and eicosapentaenoic acid, have been associated with an increased risk of various mental disorders. However, the findings of randomised clinical trials investigating therapeutic effects of omega-3 PUFAs in psychiatric disorders are inconclusive, which limits their use in clinical practice. High-quality clinical trials need to be conducted in order to assess the efficacy of omega-3 PUFAs in the prevention and treatment of mental disorders. Unwanted side effects of omega-3 PUFA supplementation should be considered. These may become apparent many years after administration and therefore elude detection.
... It has also been reported that adequate n-3 PUFA intake affects mood disorders, with improvements in uni-and bipolar depression. 84 There is an inverse relationship between n-3 PUFA concentration in the plasma and risk of psychological distress. 85,86 In terms of differences in national dietary practices, low intake of fish and seafood has been associated with a higher national prevalence of depression and schizophrenia. ...
Article
The performance of the human brain is based on an interplay between the inherited genotype and external environmental factors, including diet. Food and nutrition, essential in maintenance of brain performance, also aid in prevention and treatment of mental disorders. Both the overall composition of the human diet and specific dietary components have been shown to have an impact on brain function in various experimental models and epidemiological studies. This narrative review provides an overview of the role of diet in 5 key areas of brain function related to mental health and performance, including: (1) brain development, (2) signaling networks and neurotransmitters in the brain, (3) cognition and memory, (4) the balance between protein formation and degradation, and (5) deteriorative effects due to chronic inflammatory processes. Finally, the role of diet in epigenetic regulation of brain physiology is discussed.
... A 2014 systematic study was able to show a connection between unhealthy eating patterns and poorer mental health in both children and adolescents (O'Neil et al., 2014). Similarly, in older adults, it was found when nutrition counseling was provided, it was as effective as psychotherapy in deterring depression (Freeman et al., 2006). Although much more studies of the impact of omega-3 fatty acids on mental health are needed, these essential fatty acids have also been shown to reduce inflammation and reduce the risk of cardiovascular disease and other chronic diseases and some cancers (De Lorgeril & Salen, 2008). ...
Article
Poor dietary choices can lead to chronic physical illnesses and mental health issues. Nutrition and mental health have gained more attention recently, with a greater focus on complex nutrition at the biological level. Social workers have not traditionally taken an active role in direct discussion of nutrition with clients, but with the need for translation of complicated nutrition information, social workers should gain a broader understanding of nutrition for assessment and intervention.
... Past reviews on certain nutrients and their affiliation to depression focus on a single or group of nutrients, such as polyunsaturated fatty acids (PUFAs). [3] However, research evidence concerning whether nutritional factors control the risk of perinatal depression is still unconvincing. There is need for additional longitudinal studies with strong and consistent measurement of dietary intake and symptoms of depression, if possible, beginning right before pregnancy. ...
Article
Depression is a major public health issue concerning many women during and after pregnancy. Most research studies indicate a prospective role of zinc in decreasing or inhibiting such depressive indications. Several investigations have evaluated the link between low zinc levels and depression. However, there are limited clinical trials examining zinc supplementation in depressed women before and after pregnancy. As a result, the review put together findings from some of the published studies on the effectiveness of zinc supplementation in the reduction or deterrence of depressive symptoms. Studies discussed in this paper were searched on Pubmed. In some of the studies, support for the effectiveness of zinc supplements on depressive indications was noted. However, in most of the studies, zinc supplementation was used as an adjunct of antidepressants drug treatment and was found to lower depressive symptoms significantly. The current study is limited in various ways. Currently, there are only a few trials investigating the impact of women taking zinc supplements to alleviate depressive symptoms before and after pregnancy. It is not possible to upgrade this review into a systematic review since a general pooled estimation of effect cannot be determined. In summary, it was evident from this review that zinc supplementation has potential benefits for depression, either as an independent intervention or as an addition to traditional antidepressant drug therapy. Even so, existing studies have several methodological challenges and there is need for additional well-designed studies evaluating zinc supplementation during pregnancy and post-delivery care to prevent postpartum depression.
... blood pressure, platelet reactivity, thrombosis, cardiac arrhythmia, and the risk of sudden cardiac death, heart rate variability, and inflammation [33][34][35][36]. Further, EPA and DHA have a protective effect in mood disorders [37] and can reduce symptoms in patients with depression [38][39][40][41]. Brain function is also affected by DHA; low levels of DHA have been found in the brains of persons suffering from Alzheimer's disease. ...
Article
Full-text available
Plukenetia volubilis (Euphorbiaceae) is an underutilized oilseed crop native to the Amazon basin, where it has been utilized by humans since Incan times. The large seeds contain approximately 45–50% lipid, of which approximately 35.2–50.8% is α-linolenic acid (C18:3 n-3, ω-3) and approximately 33.4–41.0% is linoleic acid (C18:2 n-6, ω-6), the two essential fatty acids required by humans. The seeds also contain 22–30% protein and have antioxidant properties. Due to its excellent nutritional composition and good agronomic properties, it has attracted increasing attention in recent years, and cultivation is expanding. When considering current global challenges, a reformation of our food systems is imperative in order to ensure food security, mitigation of climate change, and alleviation of malnutrition. For this purpose, underutilized crops may be essential tools which can provide agricultural hardiness, a reduced need for external inputs, climate resilience, diet diversification, and improved income opportunities for smallholders. Plukenetia volubilis is a promising up and coming crop in this regard and has considerable potential for further domestication; it has an exceptional oil composition, good sensory acceptability, is well suited for cultivation, and has numerous potential applications in, e.g., gastronomy, medicine, and cosmetics.
... 18 A small double-blind randomized control trial showed reduced stereotypy and hyperactivity in children with ASD after 6 weeks of omega 3 therapy. 19 Open labeled studies have shown significant improvement in social awareness and attention after 12 weeks of supplementation [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] but no significant changes could be deduced from other blind trials. 21,22 Some case studies have reported improvement in the core symptoms of asd on supplementation for an extended period of time. ...
Article
Autism is characterized by deficits in verbal and nonverbal communication and repetitive behaviors. There is a lack of data available regarding pharmacological treatment in autism spectrum disorders.
... Lipids rich in Polyunsaturated fatty acids fight against thrombotic, aging, cholesterelemic, inflammatory and cancer like disorders and act as inhibitory drugs which further stimulate immune system as well as used as immunosuppressant therapeutics [28]. EPA and DHA (Omega-3 fatty acids) are also helpful as of the prevention from neuropsychiatric illness [29]. Subsequently, the probability of fish waste selection as compared to muscle for lipid extraction is inexpensive source which could prospectively make remarkable profits for environment and fish processing industries. ...
Article
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Fish production and fish processing waste have straight connection. In India, the waste produced during the processing of fish is predicted to be approximate 3.6 million metric tonnes, 48 per cent of the total body weight of Indian and exotic major carps is thrown away as waste (non-edible). The present research, it was conducted to compare the total lipid content (TLC) and fatty acid composition from the liver of captured and cultured fish, Labeo rohita (Hamilton) having weight more than 500 gram during different months as well as to evaluate its nutritional quality. Maximum total lipid content (33.33±0.14%) was found in the liver of cultured fish in May month, while the minimum (15.26±0.24%) was in the liver of captured fish in the month of January. During the study, total lipid content was found to be considerably elevated in cultured than captured Fish, Labeo rohita (Hamilton). The amount of three major groups of fatty acids namely polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids was found to be maximum in captured Original Research Article Brraich et al.; JPRI, 33(44B): 398-408, 2021; Article no.JPRI.74144 399 fish during the month of March 97.19±0.96%, 61.30±0.56% and 95.39±0.31% month of April respectively. Total n-6 polyunsaturated fatty acids were observed to be highest (21.95±8.05%) in the waste of liver in cultured fish during the month of March. Hence, it is concluded that the processing waste (liver) of the captured and cultured, Labeo rohita (Hamilton) is a prosperous resource of the essential fatty acids i.e. PUFAs and total lipids. Further, it is observed that captured species are rich in fatty acid composition as compared to cultured species. Food industries can manufacture by-products from these high nutritional value contents of waste for human utilization. EPA and DHA also reduce the risk of various life threatening diseases.
... Psychiatry studies investigated the association between depression and omega-3 fatty acid as a potential complementary and well-tolerated intervention for cancer patients suffering from depression [38]. Several meta-analyses have reported positive outcomes for omega-3 fatty acids in the treatment of depression [40][41][42][43], although a Cochrane review concluded that overall results are not unanimously positive [44]. ...
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Background Research exploring the use of specific Complementary and Alternative Medicine (CAM) modalities by Norwegian cancer patients is sparse. The aims of this study were therefor to map the different CAM modalities cancer patients use and further investigate their rationale for use, communication about use, self-reported benefits and harms, and their sources of information about the different modalities. Methods In cooperation with the Norwegian Cancer Society (NCS), we conducted an online cross-sectional study among members of their user panel with present or previously cancer (n = 706). The study was carried out in September/October 2021 using a modified cancer-specific version of the International Questionnaire to Measure Use of Complementary and Alternative Medicine (I-CAM-Q). In total, 468 members, 315 women and 153 men, agreed to participate resulting in a response rate of 67.2%. The study was reported in accordance with the National Research Center in Complementary and Alternative Medicine’s (NAFKAM) model of reporting CAM use. Results A large proportion of the participants (79%, n = 346) had used some form of CAM with a mean of 3.8 modalities each (range 1-17); 33% (n = 143) had seen a CAM provider, 52% (n = 230) had used natural remedies, while 58% (n = 253) had used self-help practices. Most of the participants used CAM to increase their quality of life, cope with the cancer disease or for relaxation/well-being (64%-94%), mostly with high satisfaction and low rates of adverse effects. Few used CAM to treat cancer or prevent it from spreading (16%, n = 55). The main information sources were health care providers (47%), the internet (47%), and family and friends (39%). More than half (59%) of the cancer patients discussed their use of at least one CAM modality with a physician. Conclusions The results of this survey will provide health professionals with more in-depth insight into the patterns of CAM use by cancer patients and facilitate better-informed discussions with their patients. Considering the high use of CAM, reliable information provision supporting cancer care providers’ knowledge and health literacy among patients as well as good communication are crucial. The cooperation between the NCS and NAFKAM provides an example of how to address these issues.
... Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3-(n-3) polyunsaturated fatty acids (PUFAs) found mainly in fatty fishes (such as sardines, mackerel, herring, tuna, salmon, and trout) and fish oils. A diet high in PUFAs is beneficial to maintaining healthy blood cholesterol levels which can significantly reduce cardiovascular risk, 378 as well as promote therapeutic effects against colon cancer 379 and neuropsychiatric disorders including PTSD [380][381][382][383] ; EPA and DHA were both decreased in the plasma of subjects with PTSD, 367 attributed to the induction of oxidative stress by elevated cortisol levels. 384 These PUFAs act at the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) and retinoid X receptors to modulate immune responses by inhibiting nuclear factorkappa B (NF-κB) signaling, and suppressing the synthesis and release of the pro-inflammatory cytokines cyclooxygenase-2 (COX-2), IL-6, IL-1β, inducible nitric oxide synthase (iNOS), and TNF-α. ...
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Biomarkers of PTSD are greatly needed because of the challenges to diagnose and treat due to stigma, biases in self-reporting, and limitations of identifying those at risk and the scarcity of tools to predict treatment outcome. PTSD is influenced by both genetic and environmental factors as well as its interplay. Because of the dynamic and context-dependent nature of epigenetic modifications, these offer great promise as biomarkers of PTSD for the prevention, prognosis, and prediction of treatment outcome. In this chapter, genomic and epigenomic studies of PTSD are discussed. Epigenomic studies of PTSD conducted to date include DNA methylation (including DNA methylation age), histone modifications, and noncoding RNAs. Further, we discuss recent work using integrative multiomics approach as well as related gaps, challenges, and future directions aimed at identifying biomarkers of PTSD.
... These fatty acids make important contributions to the function of the brain and the nervous system (23,24). It has been stated that adequate EPA intake is important as an adjuvant treatment for depression and mental health in general (25). ...
... Similarly, administration of DHA and/or EPA to pregnant and/or postpartum women did not result in a decrease in symptoms of depression [118][119][120][121] Clinical trials of n-3 PUFAs have been conducted in patients with the diagnosis of depression. Randomized treatment with n-3 PUFAs in the form of fish oil, EPA and/or DHA compared to placebo showed a reduction in symptoms in patients with depression [11,54,92,107,[122][123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138]. Patients with major depression and elevations in inflammatory biomarkers showed a stronger response to EPA (but not DHA) treatment compared to depressed patients without elevations in inflammatory biomarkers [94]. ...
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Polyunsaturated fatty acids (PUFAs) are essential for brain development and function. Increasing evidence has shown that an imbalance of PUFAs is associated with various human psychiatric disorders, including autism and schizophrenia. However, the mechanisms underlying the effects of PUFAs on brain functions at cellular and molecular levels remain unclear. Since PUFAs are insoluble in water, specific transporters are required to deliver PUFAs to appropriate intracellular compartments. Fatty acid-binding proteins (FABPs), the cellular chaperones of PUFAs, are involved in PUFA intracellular trafficking, signal transduction, and gene transcription. Therefore, we focused on the relationship between FABP-regulated PUFA homeostasis in the brain and neuronal plasticity. The authors previously reported that FABP3, which preferentially binds to n-6 PUFAs, is strongly expressed in the gamma-aminobutyric acid (GABAergic) inhibitory interneurons of the adult mouse anterior cingulate cortex (ACC), which is a component of the limbic cortex and is important for the coordination of cognitive and emotional behaviors. Interestingly, Fabp3 KO mice show increased GABA synthesis and abnormal excitatory/inhibitory balance in the ACC. In addition, studies have indicated that FABP7, which preferentially binds to n-3 PUFAs, controls lipid raft function in astrocytes, and astrocytic Fabp7 deficiency results in an altered response of astrocytes to external stimuli. Furthermore, Fabp7 KO mice exhibit aberrant dendritic morphology, and decreased spine density and excitatory synaptic transmission in pyramidal neurons. This review summarizes relationship between PUFAs or FABPs and human psychiatric disorders and discusses recent progress in elucidating the function of FABPs, especially FABP3 and 7, in the brain.
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Posttraumatic stress disorder (PTSD) is an acquired, debilitating, psychiatric disorder characterized by functionally deficient physiological and psychological symptoms in the aftermath of a traumatic event. This chapter emphasizes the critical role of pharmacoepigenetics in addressing the interindividual variability seen in patients treated with current medications for trauma- and stress-related neuropsychiatric disorders such as PTSD, and highlights the scarcity of effective drugs for treating the symptoms of patients with these disorders. Chronic PTSD treatment is complicated by comorbid symptomatology, and attempts to suppress traumatic memories, for example, remain difficult. As the epigenome can either modulate drug response or be pharmacologically regulated, we underline the importance of epigenetic-based interventions for alleviating PTSD pathogenesis. We hypothesize that selective epigenetic machinery targeting with epidrugs and/or epinutraceuticals could be a viable strategy to mitigate trauma- and stress-related neuropsychiatric disorders. Furthermore, compelling evidence has linked immune system dysregulation to abnormal neuronal signaling and psychiatric disorders. However, much effort is required to transform and advance our understanding of PTSD and comorbid disorders so that new and innovative interventions for those suffering from this critical neuropsychiatric illness can be developed.
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Importance Marine omega-3 fatty acid (omega-3) supplements have been used to treat depression but their ability to prevent depression in the general adult population is unknown. Objective To test effects of omega-3 supplementation on late-life depression risk and mood scores. Design, Setting, and Participants A total of 18 353 adults participated in the VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention) ancillary study to VITAL, a randomized trial of cardiovascular disease and cancer prevention among 25 871 US adults. There were 16 657 at risk of incident depression (no previous depression) and 1696 at risk of recurrent depression (previous depression, but not for the past 2 years). Randomization occurred from November 2011 through March 2014; randomized treatment ended on December 31, 2017. Interventions Randomized 2 × 2 factorial assignment to vitamin D3 (2000 IU/d), marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid and 375 mg of docosahexaenoic acid) or placebo; 9171 were randomized to omega-3 and 9182 were randomized to matching placebo. Main Outcomes and Measures Prespecified coprimary outcomes were risk of depression or clinically relevant depressive symptoms (total of incident + recurrent cases); mean difference in mood score (8-item Patient Health Questionnaire [PHQ-8] depression scale). Results Among 18 353 participants who were randomized (mean age, 67.5 [SD, 7.1] years; 49.2% women), 90.3% completed the trial (93.5% among those alive at the end of the trial); the median treatment duration was 5.3 years. The test for interaction between the omega-3 and the vitamin D agents was not significant (P for interaction = .14). Depression risk was significantly higher comparing omega-3 (651 events, 13.9 per 1000 person-years) with placebo (583 events, 12.3 per 1000 person-years; hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P = .03). No significant differences were observed comparing omega-3 with placebo groups in longitudinal mood scores: the mean difference in change in PHQ-8 score was 0.03 points (95% CI, −0.01 to 0.07; P = .19). Regarding serious and common adverse events, the respective prevalence values in omega-3 vs placebo groups were major cardiovascular events (2.7% vs 2.9%), all-cause mortality (3.3% vs 3.1%), suicide (0.02% vs 0.01%), gastrointestinal bleeding (2.6% vs 2.7%), easy bruising (24.8% vs 25.1%), and stomach upset or pain (35.2% vs 35.1%). Conclusions and Relevance Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with omega-3 supplements compared with placebo yielded mixed results, with a small but statistically significant increase in risk of depression or clinically relevant depressive symptoms but no difference in mood scores, over a median follow-up of 5.3 years. These findings do not support the use of omega-3 supplements in adults to prevent depression. Trial Registration ClinicalTrials.gov Identifiers: NCT01696435 and NCT01169259
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Participants, methods, and results We obtained data from the PAQUID (Personnes Agées QUID) epidemiological study of cognitive and functional ageing (www.healthandage.net/html/min/paquid/entrance.htm). During the third wave of the study (1991-2) investigators visited 1674 people aged 68 and over without dementia and living at home in 75 parishes in southwestern France and recorded their frequency of consumption of meat and fish or seafood: daily, at least once a week (but not every day), from time to time (but not every week), never. Participants were followed up two, five, and seven years afterwards: 1416 (84.6 %) had at least one follow up visit. All the participants who had lost three points or more on the mini-mental state examination since a previous visit or were suspected of having dementia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R) were visited by a neurologist to confirm the diagnosis. We calculated the incidence of dementia per 100 person years. We used a Cox proportional hazards model with delayed entry to estimate the relative risk of dementia, taking into account age, sex, and education (at least the French primary school diploma “Certificat d'Etudes Primaires” versus less education3). During the seven years of follow up 170 new cases of dementia occurred, including 135 cases of Alzheimer's disease. The table shows a significant trend between increasing consumption of fish or seafood and decreasing incidence of dementia (P for trend=0.0091). Frequency of fish or seafood consumption was higher in the participants with higher education (879/1051 (83.6%) v262/365 (71.8%) consuming fish at least weekly; P<0.0001). Participants who ate fish or seafood at least once a week had a significantly lower risk of being diagnosed as having dementia in the seven subsequent years (age and sex adjusted hazard ratio 0.66, 95% confidence interval 0.47 to 0.93). When we added education into the model the hazard ratio was almost unchanged (0.73) but the 95% confidence interval (0.52 to 1.03) slightly overlapped 1.00, indicating that the “protective” effect of weekly fish or seafood consumption was partly explained by higher education of regular consumers. Participants who ate fish or seafood at least once a week had a hazard ratio, adjusted for age and sex, of 0.69 for developing Alzheimer's disease in the seven following years, with borderline significance (95% confidence interval 0.47 to 1.01). We found no significant association between meat consumption and risk of dementia—P for trend=0.59; age and sex adjusted hazard ratio for weekly consumers 0.56 (0.26 to 1.20). View this table:View PopupView InlineIncidence of dementia according to fish and meat consumption in elderly people in southwestern France Comment Elderly people who eat fish or seafood at least once a week are at lower risk of developing dementia, including Alzheimer's disease. The Rotterdam study found similar results but had a much shorter follow up (mean 2.1 years).4 Given that the first consequences of dementia on everyday living can appear three years before diagnosis,5 poor dietary habits could be a consequence rather than a cause of cognitive decline in the Rotterdam participants. In addition to providing vascular protection, the n-3 fatty acids contained in fish oils could reduce inflammation in the brain and may have a specific role in brain development and regeneration of nerve cells.2 Healthy dietary habits acquired in infancy could be associated with achievement of higher education. Highly educated people might also adhere more closely to dietary recommendations on fish consumption. Acknowledgments Contributors: PBG is co-manager of the PAQUID project and developed the concept of the study, contributed to the study design, statistical analyses, and interpretation of data, and wrote the paper. LL contributed to statistical analyses, interpretation of data, and revising the paper critically. VD contributed to the conception, data analysis, and critical review of the paper. KP contributed to data analysis and critical review of the paper. JFD is the other co-manager of the PAQUID project and contributed to the study design, interpretation of the data, and critical review of the paper. SR contributed to the conception, interpretation of the data, and critical review of the paper. All authors approved the final version. PBG is the guarantor. Footnotes Funding Association pour la Recherche Médicale en Aquitaine (Bordeaux), Caisse Nationale d'Assurance Maladie des Travailleurs Salari's, Conseil Général de la Dordogne, Conseil Général de la Gironde, Conseil Régional d'Aquitaine, Fondation de France, France Alzheimer (Paris), Institut National de la Santé et de la Recherche Médicale, Mutuelle Générale de l'Education Nationale, Mutualité Sociale Agricole, Novartis Pharma (France), SCOR Insurance (France). Conflict of interest None declared.References1.Grant WB.Dietary links to Alzheimer's disease: 1999 update.J Alzheimer Dis 1999; 1:197–201.OpenUrl2.↵Kalmijn S.Fatty acid intake and the risk of dementia and cognitive decline: a review of clinical and epidemiological studies.J Nutr Health Aging 2000; 4:202–207.OpenUrlMedline3.↵Letenneur L, Gilleron V, Commenges D, Helmer C, Orgogozo JM, Dartigues JF.Are sex and educational level independent predictors of dementia and Alzheimer's disease? Incidence data from the PAQUID project.J Neurol Neurosurg Psychiatry 1999; 66:177–183.OpenUrlFREE Full Text4.↵Kalmijn S, Launer LJ, Ott A, Witteman JCM, Hofman A, Breteler MMB.Dietary fat intake and the risk of incident dementia in the Rotterdam study.Ann Neurol 1997; 42:776–782.OpenUrlCrossRefMedlineWeb of Science5.↵Barberger-Gateau P, Fabrigoule C, Helmer C, Rouch I, Dartigues JF.Functional impairment in instrumental activities of daily living: an early clinical sign of dementia?J Am Geriatr Soc 1999; 47:456–462.OpenUrlMedline
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The use of various dietary supplements containing fish oils has become popular as a method of reducing the risk of developing cardiovascular disease. However, consumption of large amounts of these substances may pose some potential hazards. Described herein is a patient who developed hypervitaminosis A after prolonged fish oil supplement ingestion.
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Attention-deficit hyperactivity disorder (ADHD) is the term used to describe children who are inattentive, impulsive, and hyperactive. The cause is unknown and is thought to be multifactorial. Based on the work of others, we hypothesized that some children with ADHD have altered fatty acid metabolism. The present study found that 53 subjects with ADHD had significantly lower concentrations of key fatty acids in the plasma polar lipids (20:4n-6, 20:5n-3, and 22:6n-3) and in red blood cell total lipids (20:4n-6 and 22:4n-6) than did the 43 control subjects. Also, a subgroup of 21 subjects with ADHD exhibiting many symptoms of essential fatty acid (EFA) deficiency had significantly lower plasma concentrations of 20:4n-6 and 22:6n-3 than did 32 subjects with ADHD with few EFA-deficiency symptoms. The data are discussed with respect to cause, but the precise reason for lower fatty acid concentrations in some children with ADHD is not clear.
Article
Although inconsistencies exist, some studies have shown that meat consumption is associated with breast cancer risk. Several heterocyclic amines (HAs), formed in the cooking of meats, are mammary carcinogens in laboratory models. HAs are activated by polymorphic N‐acetyltransferase (NAT2) and rapid NAT2 activity may increase risk associated with HAs. We investigated whether ingestion of meat, chicken and fish, as well as particular concentrated sources of HAs, was associated with breast cancer risk, and if NAT2 genotype modified risk. Caucasian women with incident breast cancer (n = 740) and community controls (n = 810) were interviewed and administered a food frequency questionnaire. A subset of these women (n = 793) provided a blood sample. Polymerase chain reaction and restriction fragment length polymorphism analyses were used to determine NAT2 genotype. Consumption of red meats, as well as an index of concentrated sources of HAs, was not associated with increased breast cancer risk, nor did risk vary by NAT2 genotype. In post‐menopausal women, higher fish consumption was inversely associated with risk (odds ratio = 0.7; 95% confidence interval, 0.4–1.0); among pre‐menopausal women, there was the suggestion of inverse associations between risk and pork and chicken intake. Our results suggest that consumption of meats and other concentrated sources of HAs is not associated with increased breast cancer risk. However, due to the strong biologic plausibility for a role of some HAs in mammary carcinogenesis, and the likely measurement error in evaluation of sources of HAs in this study, further studies of these possible relationships are warranted. Int. J. Cancer75:825–830, 1998. Published 1998 Wiley‐Liss, Inc.
Article
Several sources of information suggest that man evolved on a diet with a ratio of ω6 to ω3 fatty acids of ∼ 1 whereas today this ratio is ∼10:1 to 20–25:1, indicating that Western diets are deficient in ω3 fatty acids compared with the diet on which humans evolved and their genetic patterns were established. Omega-3 fatty acids increase bleeding time; decrease platelet aggregation, blood viscosity, and fibrinogen; and increase erythrocyte deformability, thus decreasing the tendency to thrombus formation. In no clinical trial, including coronary artery graft surgery, has there been any evidence of increased blood loss due to ingestion of ω3 fatty acids. Many studies show that the effects of ω3 fatty acids on serum lipids depend on the type of patient and whether the amount of saturated fatty acids in the diet is held constant. In patients with hyperlipidemia, ω3 fatty acids decrease low-density-lipoprotein (LDL) cholesterol if the saturated fatty acid content is decreased, otherwise there is a slight increase, but at high doses (32 g) they lower LDL cholesterol; furthermore, they consistently lower serum triglycerides in normal subjects and in patients with hypertriglyceridemia whereas the effect on high-density lipoprotein (HDL) varies from no effect to slight increases. The discrepancies between animal and human studies most likely are due to differences between animal and human metabolism. In clinical trials eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of fish oils along with antirheumatic drugs improve joint pain in patients with rheumatoid arthritis; have a beneficial effect in patients with ulcerative colitis; and in combination with drugs, improve the skin lesions, lower the hyperlipidemia from etretinates, and decrease the toxicity of cyclosporin in patients with psoriasis. In various animal models ω3 fatty acids decrease the number and size of tumors and increase the time elapsed before appearance of tumors. Studies with nonhuman primates and human newborns indicate that DHA is essential for the normal functional development of the retina and brain, particularly in premature infants. Because ω3 fatty acids are essential in growth and development throughout the life cycle, they should be included in the diets of all humans. Omega-3 and ω6 fatty acids are not interconvertible in the human body and are important components of practically all cell membranes. Whereas cellular proteins are genetically determined, the polyunsaturated fatty acid (PUFA) composition of cell membranes is to a great extent dependent on the dietary intake. Therefore appropriate amounts of dietary ω6 and ω3 fatty acids need to be considered in making dietary recommendations, and these two classes of PUFAs should be distinguished because they are metabolically and functionally distinct and have opposing physiological functions. Their balance is important for homeostasis and normal development. Canada is the first country to provide separate dietary recommendations for ω6 and ω3 fatty acids.
Article
Objective: The aim of this study was to assess whether self-reported mental health status, measured using the SF-36 questionnaire, was associated with fish consumption, assessed using a food-frequency questionnaire. Design: The cross-national data were collected in the 1996/97 New Zealand Health Survey and 1997 Nutrition Survey, which were conducted using the same sampling frame. Survey respondents were categorised into those who consumed no fish of any kind and those who consumed some kind of fish, at any frequency. Data were adjusted for age, household income, eating patterns, alcohol use and smoking. Other demographic variables and potential confounding nutrients were included in the preliminary analyses but were not found to have a significant relationship with fish consumption. Subjects: Data from a nationally representative sample of 4644 New Zealand adults aged 15 years and over were used in this analysis. Results: Fish consumption was significantly associated with higher self-reported mental health status, even after adjustment for possible confounders. Differences between the mean scores for fish eaters and those who never eat fish were 8.2 for the Mental Health scale (P = 0.005) and 7.5 for the Mental Component score (P = 0.001). Conversely, the association between fish consumption and physical functioning was in the opposite direction (P = 0.045). Conclusions: This is the first cross-sectional survey to demonstrate a significant relationship between fish intake and higher self-reported mental health status, therefore offering indirect support for the hypothesis that omega-3 polyunsaturated fatty acids may act as mood stabilisers.
Article
Attention-deficit/Hyperactivity Disorder (AD/HD) is the diagnosis used to describe children who are inattentive, impulsive, and hyperactive. AD/HD is the most common childhood behavioral disorder affecting 3 to 5 percent of the scnool-age population. In most children with AD/HD, the cause is unknown, but is thought to be multifactorial. In an earlier study, we reported that subjects with AD/HD who also had symptoms indicative of essential fatty acid (EFA) deficiency had lower levels of 20:4n-6, 20:5n-3 and 22:6n-3 fatty acids than control subjects and those subjects with AD/HD showing no symptoms indicative of EFA deficiency (Am. J. Clin. Nutr. 1995:62:761-8). The purpose of the study reported here was to compare the relationship between n-3 and n-6 fatty acid status and the severity of behavior, learning, and health problems in the population of subjects reported in the previous study. All subjects (both AD/HD and control) were included and divided into three groups based on their total plasma polar lipid fatty acid values. A contrast analysis between high and low n-3 and n-6 fatty acid levels and behavior, learning and health measures was performed. Subjects with lower total n-3 fatty acid levels showed a significantly greater number of behavior problems, assessed by the Gönners' Rating Scale, as well as temper tantrums, learning, health, and sleep problems. Very few contrast comparisons were significantly different with respect to total n-6 fatty acid levels. Only more colds and more antibiotic use were reported by those subjects with lower total n-6 fatty acids. These findings parallel the results of recent reports on the behavioral effects of n-3 fatty acid deficiency in experimentally deprived animals.
Article
n-3 Fatty acids may reduce the incidence of sudden cardiac death, a property potentially related to their activity on myocardial excitability. We carried out a cross-over trial in which 10 coronary patients were treated with n-3 ethyl esters at two different dosages (3 and 6 g day ⁻¹) for 4 weeks. Plasma fatty acid composition, lipid profile, and heart rate variability (HRV) were analysed. n-3 Fatty acid intake significantly reduced plasma cholesterol and triglyceride levels and decreased the low to high frequency ratio. In addition, significant positive correlations were found between n-3 phospholipid content and HRV indices, thus confirming, in a prospective trial, retrospective data suggesting that an increased HRV may be achieved in coronary patients by exogenous provision of n-3 fatty acids.
Article
Objective: To investigate the relation between maternal fish intake in late pregnancy and the frequency of low birth weight and intrauterine growth retardation (IUGR). Participants: 11 585 pregnant women in south west England. Methods: Information on fish intake was obtained from a food frequency questionnaire sent to the women at 32 weeks’ gestation, and used to calculate n-3 fatty acid (n-3FA) intake from fish. IUGR was defined as a birth weight for gestational age and sex below the 10th centile. Confounding variables considered included maternal age, height, weight, education, parity, smoking and drinking in pregnancy, and whether the mother was living with a partner. Only singleton, liveborn infants were included. Main results: Mean daily intakes of fish and n-3FAs were 32.8 g and 0.147 g respectively. In unadjusted analyses there were positive associations between mean birth weight and fish intake or n-3FA intake, but these disappeared on adjustment for potential confounders. The frequency of IUGR decreased with increasing fish intake—the OR (95%CI) of IUGR in those eating no fish was 1.85 (1.44 to 2.38) compared with those in the highest fish intake group. On adjustment this relation was attenuated (adjusted OR 1.37 (1.02 to 1.84)), but the decline in the frequency of IUGR with increasing fish intake remained statistically significant. No relation was observed between mean gestation and fish or n-3FA intake. Conclusions: These results lend some support to the hypothesis that raising fish or n3-FA intake during pregnancy may increase fetal growth rate. However, they provide no evidence that increasing fish consumption is associated with an increase in mean gestation.
Article
Background ω3 Fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate, 2 effective treatments for bipolar disorder. The present study was performed to examine whether ω3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder. Methods A 4-month, double-blind, placebo-controlled study, comparing ω3 fatty acids (9.6 g/d) vs placebo (olive oil), in addition to usual treatment, in 30 patients with bipolar disorder. Results A Kaplan-Meier survival analysis of the cohort found that the ω3 fatty acid patient group had a significantly longer period of remission than the placebo group (P=.002; Mantel-Cox). In addition, for nearly every other outcome measure, the ω3 fatty acid group performed better than the placebo group. Conclusion ω3 Fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder.
Article
Background: It has been hypothesized that depletion of cell membrane n3 polyunsaturated fatty acids (PUFA), particularly docosahexanoic acid (DHA), may be of etiological importance in depression. Methods: We measured the fatty acid composition of phospholipid in cell membranes from red blood cells (RBC) of 15 depressive patients and 15 healthy control subjects. Results: Depressive patients showed significant depletions of total n3 PUFA and particularly DHA. Incubation of RBC from control subjects with hydrogen peroxide abolished all significant differences between patients and controls. Conclusions: These findings suggest that RBC membranes in depressive patients show evidence of oxidative damage. Possible interpretations, and implications for the etiology and treatment of depression, are discussed.
Article
Dietary intakes of specific polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid, and the ratio between omega-6 and omega-3 consumption during pregnancy and lactation affect maternal and infant PUFA status and may play a role in infant neurodevelopment. The 1994–1996 U.S. Department of Agriculture/ARS Continuing Survey of Food Intakes by Individuals, a nationally representative analysis of consumption, provides data on the five major PUFAs in the food supply, including intakes from a subset of 112 pregnant or lactating women. Mean individual daily intakes of omega-6 fats are more than 200% of recommended upper limits proposed by a recent National Institutes of Health workshop, and intakes of omega-3 fats are only 20–60% of recommended adequate intakes.Intakes of omega-3, eicosapentaenoic acid, and docosahexaenoic acid are highest in women older than 40 years of age, those of Asian/Pacific descent, households with income greater than 350% of the poverty level, and women with at least 1 year of college education. Finally, PUFA intakes are compared with intakes in other countries, with U.S. consumption of omega-6 higher and omega-3 lower than those in Japan and several other European nations. PUFAMean daily intake (g)NIH Workshop recommendation (g/d)Linoleic acid14.1486.67Arachidonic acid0.118Linolenic acid1.4072.22Eicosapentaenoic acid0.0220.22Docosahexaenoic acid0.0540.30
Article
Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs), including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue contents (red blood cell membrane, plasma, etc.) and dietary intake. However, more evidence is needed to support its relation. In this study, we conducted an 8-week, double-blind, placebo-controlled trial, comparing omega-3 PUFAs (9.6 g/day) with placebo, on the top of the usual treatment, in 28 patients with major depressive disorder. Patients in the omega-3 PUFA group had a significantly decreased score on the 21-item Hamilton Rating Scale for Depression than those in the placebo group (P
Article
Depression is associated with a lowered degree of esterification of serum cholesterol, an increased C20:4ω6/C20:5ω3 ratio and decreases in ω3 fractions in fatty acids (FAs) or in the red blood cell membrane. The aims of the present study were to examine: (i) serum phospholipid and cholesteryl ester compositions of individual saturated fatty acids (SFAs), monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs) in major depressed patients vs. healthy volunteers; (ii) the relationships between the above FAs and lowered serum zinc (Zn), a marker of the inflammatory response in depression; and (iii) the effects of subchronic treatment with antidepressants on FAs in depression. The composition of the FAs was determined by means of thin layer chromatography in conjunction with gas chromatography. Lipid concentrations were assayed by enzymatic colorimetric methods. The oxidative potential index (OPI) of FAs was computed in 34 major depressed inpatients and 14 normal volunteers. Major depression was associated with: increased MUFA and C22:5ω3 proportions and increased C20:4ω6/C20:5ω3 and C22:5ω6/C22:6ω3 ratios; lower C22:4ω6, C20:5ω3 and C22:5ω3 fractions in phospholipids; lower C18:3ω3, C20:5ω3 and total (Σ)ω3 FAs, and higher C20:4ω6/C20:5ω3 and Σω6/Σω3 ratios in cholesteryl esters; lower serum concentrations of phospholipids and cholesteryl esters; and a decreased OPI. In depression, there were significant and positive correlations between serum Zn and C20:5ω3 and C22:6ω3 fractions in phospholipids; and significant inverse correlations between serum Zn and the Σω6/Σω3, C20:4ω6/C20:5ω3, and C22:5ω6/C22:6ω3 ratios in phospholipids. There was no significant effect of antidepressive treatment on any of the FAs. The results show that, in major depression, there is a deficiency of ω3 PUFAs and a compensatory increase in MUFAs and C22:5ω6 in phospholipids. The results suggest that: (i) there is an abnormal metabolism of ω3 PUFAs in depression; (ii) the FA alterations in depression are related to the inflammatory response in that illness; and (iii) the disorders may persist despite successful antidepressant treatment.
Article
Objective: Studies have reported that countries with high rates of fish oil consumption have low rates of depressive disorder. The authors studied a specific omega-3 fatty acid, the ethyl ester of eicosapentaenoic acid (E-EPA), as an adjunct to treatment for depressive episodes occurring in patients with recurrent unipolar depressive disorder who were receiving maintenance antidepressant therapy. Method: Twenty patients with a current diagnosis of major depressive disorder participated in a 4-week, parallel-group, double-blind addition of either placebo or E-EPA to ongoing antidepressant therapy. Seventeen of the patients were women, and three were men. Results: Highly significant benefits of the addition of the omega-3 fatty acid compared with placebo were found by week 3 of treatment. Conclusions: It is not possible to distinguish whether E-EPA augments antidepressant action in the manner of lithium or has independent antidepressant properties of its own.
Article
Although inconsistencies exist, some studies have shown that meat consumption is associated with breast cancer risk. Several heterocyclic amines (HAs), formed in the cooking of meats, are mammary carcinogens in laboratory models. HAs are activated by polymorphic N-acetyltransferase (NAT2) and rapid NAT2 activity may increase risk associated with HAs. We investigated whether ingestion of meat, chicken and fish, as well as particular concentrated sources of HAs, was associated with breast cancer risk, and if NAT2 genotype modified risk. Caucasian women with incident breast cancer (n = 740) and community controls (n = 810) were interviewed and administered a food frequency questionnaire. A subset of these women (n = 793) provided a blood sample. Polymerase chain reaction and restriction fragment length polymorphism analyses were used to determine NAT2 genotype. Consumption of red meats, as well as an index of concentrated sources of HAs, was not associated with increased breast cancer risk, nor did risk vary by NAT2 genotype. In post-menopausal women, higher fish consumption was inversely associated with risk (odds ratio = 0.7; 95% confidence interval, 0.4–1.0); among pre-menopausal women, there was the suggestion of inverse associations between risk and pork and chicken intake. Our results suggest that consumption of meats and other concentrated sources of HAs is not associated with increased breast cancer risk. However, due to the strong biologic plausibility for a role of some HAs in mammary carcinogenesis, and the likely measurement error in evaluation of sources of HAs in this study, further studies of these possible relationships are warranted. Int. J. Cancer75:825–830, 1998. Published 1998 Wiley-Liss, Inc.
Article
Objective. To determine the following: 1) whether dietary supplementation with fish oil will allow the discontinuation of nonsteroidal antiinflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA); 2) the clinical efficacy of high-dose dietary ω3 fatty acid fish oil supplementation in RA patients; and 3) the effect of fish oil supplements on the production of multiple cytokines in this population. Methods. Sixty-six RA patients entered a double-blind, placebo-controlled, prospective study of fish oil supplementation while taking diclofenac (75 mg twice a day). Patients took either 130 mg/kg/day of ω3 fatty acids or 9 capsules/day of corn oil. Placebo diclofenac was substituted at week 18 or 22, and fish oil supplements were continued for 8 weeks (to week 26 or 30). Serum levels of interleukin-1β (IL-1β), IL-2, IL-6, and IL-8 and tumor necrosis factor α were measured by enzyme-linked immunosorbent assay at baseline and during the study. Results. In the group taking fish oil, there were significant decreases from baseline in the mean (±SEM) number of tender joints (5.3 ± 0.835; P < 0.0001), duration of morning stiffness (−67.7 ± 23.3 minutes; P = 0.008), physician's and patient's evaluation of global arthritis activity (−0.33 ± 0.13; P = 0.017 and −0.38 ± 0.17; P = 0.036, respectively), and physician's evaluation of pain (−0.38 ± 0.12; P = 0.004). In patients taking corn oil, no clinical parameters improved from baseline. The decrease in the number of tender joints remained significant 8 weeks after discontinuing diclofenac in patients taking fish oil (−7.8 ± 2.6; P = 0.011) and the decrease in the number of tender joints at this time was significant compared with that in patients receiving corn oil (P = 0.043). IL-1β decreased significantly from baseline through weeks 18 and 22 in patients consuming fish oil (−7.7 ± 3.1; P = 0.026). Conclusion. Patients taking dietary supplements of fish oil exhibit improvements in clinical parameters of disease activity from baseline, including the number of tender joints, and these improvements are associated with significant decreases in levels of IL-1β from baseline. Some patients who take fish oil are able to discontinue NSAIDs without experiencing a disease flare.
Article
Objective In this flexible-dose, open-label trial, we examined the efficacy of omega-3 fatty acids for the treatment of depression during pregnancy. Methods Fifteen pregnant women with major depressive episodes participated. Subjects initially received two capsules per day [0.93 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]; the dose could be increased by one capsule per day every 2 weeks to a maximal dose of 2.8 g. Subjects were assessed with the Edinburgh Postnatal Depression Scale (EPDS) and Hamilton Rating Scale for Depression (HRSD). Results Average duration of participation in this treatment trial was 8.3 weeks (SD ± 7.1). Average final dose of EPA + DHA in this flexible dose trial was 1.9 g per day (±0.5). The mean reduction in EPDS scores was 40.9% (SD ± 21.9); the mean decrease in HRSD score was 34.1% (SD ± 27.1). Conclusions This open trial provides data to support the need for randomized controlled dose-finding trials of omega-3 fatty acids in major depressive episodes during pregnancy.
Article
The regional cerebral blood flow (rCBF) response to vibrotactile stimulation was compared in conscious young (5.9±1.8 years old) and aged (18.0±3.3 years old) monkeys using [15O]H2O and high-resolution positron emission tomography (PET). In addition, the effects of docosahexaenoic acid (DAH), an n-3 polyunsaturated fatty acid (PUFA), on the rCBF response to stimulation were evaluated in aged monkeys. Soybean milk (SBM) or DHA-containing SBM (DHA/SBM) was supplied to aged monkeys for 1 and 4 weeks. Under control conditions, vibrotactile stimulation elicited an increase in the rCBF response in the contralateral somatosensory cortices of both young and aged monkeys, but the degree of increase in the rCBF response was significantly lower in aged monkeys (116% of corresponding ‘rest’ condition) than that in young animals (141%). The regional cerebral metabolic rate of glucose (rCMRglc) response to the stimulation, an index of neuronal activation, was not significantly different between young and aged monkeys as measured by [18F]-2-fluoro-2-deoxy-d-glucose (FDG). Supply of DHA/SBM at a dose of 150 mg/kg/day as DHA for 1 week resulted in a significant increase in rCBF response to stimulation (127%) in aged monkeys, and 4-week supply of DHA induced further facilitation of the rCBF response (133%). In contrast, the reduced rCBF response in the aged monkeys was not affected by SBM alone for either 1 or 4 weeks. The neuronal activation itself elicited by the stimulation, as measured by [18F]FDG, was not affected by SBM or DHA/SBM. These results suggested the involvement of DHA in the coupling mechanism between the neuronal activation and rCBF response, possibly by modulation of cholinergic neuronal transmission.
Article
There is a hypothesis that lack of n-3 polyunsaturated fatty acids (PUFAs) is of aetiological importance in depression. Docosahexaenoic acid, a member of the n-3 PUFA family, is a crucial component of synaptic cell membranes. The aim of this study was to measure RBC membrane fatty acids in a group of depressed patients relative to a well matched healthy control group. Red blood cell (RBC) membrane levels, and dietary PUFA intake were measured in 10 depressed patients and 14 matched healthy control subjects. There was a significant depletion of RBC membrane n-3 PUFAs in the depressed subjects which was not due to reduced calorie intake. Severity of depression correlated negatively with RBC membrane levels and with dietary intake of n-3 PUFAs. Lower RBC membrane n-3 PUFAs are associated with the severity of depression. Although patient numbers were small, confounding factors were well controlled for and the results were highly significant. Results of the dietary data would tend to be weakened due to the limitations associated with dietary assessment. The findings raise the possibility that depressive symptoms may be alleviated by n-3 PUFA supplementation.
Article
The effects of alpha-linolenic acid diet deficiency on rat dopaminergic metabolism were investigated in the frontal cortex of male 2-3 month-old rats using the microdialysis method. Increased basal levels of dopamine metabolites were observed in the frontal cortex of awake deficient rats, without modification of dopamine levels. Moreover, using KCl perfusion which releases newly synthesized dopamine, no difference was observed in anaesthetized deficient rats versus control rats. In addition, a decrease in dopamine release was observed in anaesthetized deficient rats versus control rats after tyramine stimulation, which is known to induce release of dopamine from vesicular stores. A working model is proposed which suggests that a chronic n-3 polyunsaturated fatty acids (PUFA) deficiency may lead to modifications in the internalization of dopamine in the storage pool in the frontal cortex.
Article
Patients suffering from endogenous depression had significantly greater proportions of long chain polyunsaturated fatty acids (LCP), docosahexaenoic acid (22:6?3) and eicosapentaenoic acid (20:5?3), and a reduced proportion of linoleic acid (18:2?6) in their plasma choline phosphoglycerides (CPG) compared with age-sex-matched healthy controls. Patients suffering from reactive depression or from other psychiatric disorders did not differ significantly from matched controls. Changes in the fatty acid composition of the major erythrocyte membrane phospholipids were in the same direction but were less marked. The importance and possible reasons for the elevated LCP in endogenous depression are discussed.
Article
The high birthweights and long duration of pregnancy in the Faroe Islands led us to suggest that a high intake of marine-fat-derived n-3 fatty acids might prolong pregnancy by shifting the balance of production of prostaglandins involved in parturition. We have compared the effects on pregnancy duration, birthweight, and birth length of a fish-oil supplement, a control olive-oil supplement, and no supplementation. 533 healthy Danish women in week 30 of pregnancy were randomly assigned in a ratio of 2/1/1 to fish oil (four 1 g Pikasol capsules [containing 2.7 g n-3 fatty acids] per day), olive oil (four 1 g capsules per day), or no supplement. The three groups differed in mean length of gestation (p = 0.006), which was highest in the fish-oil group and lowest in the olive-oil group; the result was similar when the analysis was restricted to women with an estimate of gestation length based on early ultrasound findings (443 women). Pregnancies in the fish-oil group were on average 4.0 (95% confidence interval 1.5-6.4) days longer than those in the olive-oil group; the difference in birthweight was 107 (1-214) g. The effect of supplementation on length of gestation was influenced by intake of fish and of fish oil: the difference between fish-oil and other groups was increased by a low fish intake at baseline. Fish-oil supplementation in the third trimester seems to prolong pregnancy without detrimental effects on the growth of the fetus or on the course of labour.
Article
To describe changes in negative emotions among participants of a cholesterol-lowering study. Cohort study. Quantitative evaluation of changes in negative emotions in relation to diet and plasma cholesterol levels before and after a 5-year dietary intervention program aimed at reducing plasma cholesterol levels. Community-dwelling families of the Family Heart Study, Portland, Oregon. One hundred forty-nine men and 156 women from 233 families (mean age, 37.7 years). Changes in negative emotions including depression and aggressive hostility as measured by the Hopkins Symptom Checklist (SCL-90). Improvement in overall emotional state was noted for the entire sample. Those who consumed a low-fat, high complex-carbohydrate diet at the end of the study showed significantly greater improvements in depression (P = 0.044; difference in improvement, 2.9 points) and aggressive hostility (P = 0.035; difference in improvement, 3.3 points) as well as a reduction in their plasma cholesterol levels (P = 0.024; difference in improvement, 2.7%) compared with those who ate a high-fat "American diet." Participation in a cholesterol-lowering program may not be associated with a worsening in emotional state. To the contrary, improvements in diet appear to be associated with reductions in depression and aggressive hostility as well as with lowered plasma cholesterol levels.
Article
Competition between the (n - 3) and (n - 6) types of highly unsaturated fatty acids can diminish the abundance of (n - 6) eicosanoid precursors in a tissue, which in turn can diminish the intensity of tissue responses that are mediated by (n - 6) eicosanoids. The mixture of 20- and 22-carbon highly unsaturated fatty acids maintained in the phospholipids of human plasma is related to the dietary intake of 18:2 (n - 6) and 18:3 (n - 3) by empirical hyperbolic equations in a manner very similar to the relationship reported for laboratory rats (Lands, W.E.M., Morris, A. and Libelt, B. (1990) Lipids 25, 505-516). Analytical results from volunteers ingesting self-selected diets showed an inter-individual variance for the proportion of (n - 6) eicosanoid precursors in the fatty acids of plasma phospholipids of about 5%, but the variance among multiple samples taken from the same individual throughout the day was less (about 3%), closer to the experimental variance of the analytical procedure (about 1%). The reproducibility of the results makes it likely that analysis of fatty-acid composition of plasma lipids from individuals will prove useful in estimating the diet-related tendency for severe thrombotic, arthritic or other disorders that are mediated by (n - 6) eicosanoids. Additional constants and terms were included in the equations to account for the effects of 20- and 22-carbon highly unsaturated (n - 3) fatty acids in the diet. A lower constant for the 20- and 22-carbon (n - 3) fatty acids compared to that for the 18-carbon (n - 3) fatty acid in decreasing the ability of dietary 18:2 (n - 6) to maintain 20:4 (n - 6) in tissue lipids confirmed the greater competitive effectiveness of the more highly unsaturated n - 3 fatty acids in the elongation/desaturation process. Also, a lower constant for direct incorporation of 20-carbon fatty acids of the n - 6 vs. the n - 3 type indicated a greater competitive effectiveness of 20:4 (n - 6) relative to 20:5 (n - 3) in reesterification after release from tissue lipids. The equations may be used in reverse to estimate the dietary intakes of the (n - 3) and (n - 6) fatty acids by using the composition of the fatty acids that had been maintained in plasma lipids.
Article
Dietary supplementation with omega-3 fatty acids reduces platelet aggregation in subjects who usually eat a diet low in these fatty acids. Aspirin also has an antiplatelet effect. The clinical effects of the concomitant administration of these agents were examined in this double-blind controlled crossover trial. Twelve healthy adults were randomized to supplement their diet for 21 days with 8 g of omega-3 fatty acids or identical-looking olive oil capsules. At the end of each treatment period, bleeding times were obtained before and after the administration of one 325-mg aspirin tablet. Overall, percent change in bleeding time after omega-3 fatty acid supplementation was significantly prolonged compared with olive oil supplementation before aspirin administration but not after. Bleeding times were influenced significantly by the order of randomization in the two treatment groups. Changes in post-aspirin bleeding time varied in subjects after they received olive oil. Post-aspirin bleeding times after omega-3 fatty acid supplementation were prolonged compared with baseline values but not significantly prolonged when compared with those after olive oil administration. The authors concluded that the concomitant administration of a single dose of aspirin does not prolong bleeding time in subjects who eat a diet enriched by omega-3 fatty acids versus a diet enriched by olive oil.
Article
The effects on lipoprotein and glucose metabolism of addition of n-3 fatty acids were studied in 14 non-insulin-dependent diabetic patients who were given 10 g of MaxEPA (3 g n-3 fatty acids) or placebo (olive oil) per day in a randomized double-blind cross-over study during two consecutive 8-week periods. After MaxEPA treatment, there was a marked increase in long-chain polyunsaturated fatty acids of the n-3 series in the plasma lipid esters and in the platelet phospholipids, while the n-6 fatty acid content decreased. The very low density lipoprotein (VLDL) triglyceride concentrations decreased significantly (by 22%) on MaxEPA treatment. However, these changes were not significantly different from those observed during the placebo period. The blood glucose concentration tended to increase during MaxEPA treatment, and to decrease during the placebo period, the changes under the two regimes being significantly different (P less than 0.01). In addition, the rate constant for glucose disappearance (k value) for the intravenous insulin-tolerance test, which reflected the peripheral insulin sensitivity, tended to decrease during MaxEPA treatment and increase during administration of the placebo, there being a significant difference (P less than 0.03) between the changes during the two treatments. The reason for the observed changes in blood glucose concentration and peripheral insulin sensitivity is still unclear.
Article
This study compared 48 hyperactive children with 49 age-and-sex-matched controls. Significantly more hyperactive children had auditory, visual, language, reading, and learning difficulties, and the birth weight of hyperactive children was significantly lower than that of controls (3,058 and 3,410 g, respectively; p less than 0.01). In addition, significantly more hyperactive children had frequent coughs and colds, polydypsia, polyuria, and a serious illness or accident in the past year than controls, but there was no increase in asthma, eczema, or other allergies. Serum essential fatty acid (EFA) levels were measured in 44 hyperactive subjects and 45 controls. The levels of docasahexaenoic, dihomogammalinolenic, and arachidonic acids were significantly lower in hyperactive children than controls (docosahexaenoic: 41.6 and 49.5 micrograms/ml serum respectively, p = 0.045; dihomogammolinolenic: 34.9 and 41.3 micrograms/ml serum, p = 0.007; arachidonic: 127.1 and 147.0 micrograms/ml serum, p = 0.027). These findings have possible therapeutic and diagnostic implications, but further research is needed to attempt to replicate these differences.
Article
Plasma phospholipid essential fatty acids and some of their main metabolites, prostaglandins, were measured among habitually violent and impulsive male offenders, who all had alcohol abuse problems, and nonviolent control persons. Linoleic acid (18:2n-6), the precursor of the n-6 fatty acids, was below normal in intermittent explosive disorder, but the dihomogammalinolenic acid (DGLA) (20:3n-6) and some subsequent n-6 acids were at the same time elevated among all offenders. Also, a monounsaturate, oleic acid (18:1n-9) was elevated. The high DGLA correlated with low cholesterol level in intermittent explosive disorder. The arachidonic acid metabolites PGE2 and TxB2 were elevated in violent antisocial personality. The PGE1/DGLA ratio was low in intermittent explosive disorder. The number of registered violent crimes and violent suicidal attempts correlated with high phospholipid DGLA values. The possibility that the high phospholipid DGLA is connected with low free DGLA pool, and therefore low PGE1 formation, among these offenders is discussed.