Article

Omega-3 Supplementation Lowers Inflammation in Healthy Middle-Aged and Older Adults: A Randomized Controlled Trial

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Abstract

Observational studies have linked lower levels of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) with inflammation and depression. This study was designed to determine whether n-3 supplementation would decrease serum cytokine production and depressive symptoms in 138 healthy middle-aged and older adults (average age=51.04, SD=7.76) who were sedentary and overweight (average BMI=30.59, SD=4.50). This three-arm randomized, placebo-controlled, double-blind 4-month trial compared responses to (1) 2.5 g/d n-3 PUFAs, or (2) 1.25 g/d n-3 PUFAs, or (3) placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Serum interleukin-6 decreased by 10% and 12% in our low and high dose n-3 groups, respectively, compared to a 36% increase in the placebo group. Similarly, low and high dose n-3 groups showed modest 0.2% and -2.3% changes in serum tumor necrosis factor alpha, compared to a 12% increase in the control group. Depressive symptoms were quite low at baseline and did not change significantly in response to supplementation. Our data suggest that n-3 PUFAs can reduce inflammation in overweight, sedentary middle-aged and older adults, and thus could have broad health benefits. These data provide a window into the ways in which the n-3 PUFAs may impact disease initiation, progression, and resolution. ClinicalTrials.gov identifier: NCT00385723.

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... Several markers of inflammation were assessed within the included omega-3 studies on cognition. These included interleukins (IL); IL-1b [28], IL-6 [32,44,49], IL-10 [49•], tumour necrosis factor-alpha (TNF-α) [32,38,44,49], homocysteine [26], and high-sensitivity C-reactive protein (hs-CRP) [26,36,44]. All studies were based on supplementation forms of omega-3 fatty acids only, and included six studies in healthy adults and one study in adults with MCI. ...
... Several markers of inflammation were assessed within the included omega-3 studies on cognition. These included interleukins (IL); IL-1b [28], IL-6 [32,44,49], IL-10 [49•], tumour necrosis factor-alpha (TNF-α) [32,38,44,49], homocysteine [26], and high-sensitivity C-reactive protein (hs-CRP) [26,36,44]. All studies were based on supplementation forms of omega-3 fatty acids only, and included six studies in healthy adults and one study in adults with MCI. ...
... Of the inflammatory markers reported on in these studies, no beneficial effects of omega-3 supplementation were reported for IL-1b [28], IL-10 [49•], homocysteine [26], and hs-CRP [26,36,44]. Beneficial effects were reported for all three studies on the inflammatory markers IL-6 [32,44,49], with studies ranging in duration from 4 to 6 months and with the lowest and highest cumulative dose of omega-3s (DHA plus EPA) ranging from 1216.5 mg/day to 2433 mg/day (174 mg/day DHA plus 104.2 mg/day EPA and 348 mg/day DHA and 2085 mg/ day EPA, respectively). Beneficial effects were reported in three [32,44,49] of the four studies on TNF-α, with the one study which showed no change in TNF-α having a duration of 5 weeks and dose of 1050 mg/day DHA plus 1500 mg/day EPA [38], whilst the other studies had duration and dose as given above for IL-6. ...
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Purpose of review: This review summarises previous literature and recent findings on omega-3 fatty acids in cognition and inflammation in humans, comparing the effects of dietary omega-3 with supplemental omega-3. Recent findings: Whilst some omega-3 studies, both dietary and supplementation, show positive benefits of omega-3s in cognition, particularly memory function, and supplementation studies show reduction in markers of inflammation, including IL-6 and TNF-α, some studies also show no clear benefits on cognition and inflammation, particularly in healthy populations. Most consistency in beneficial cognition outcomes has been in populations with MCI. Many clinical trials have investigated omega-3 supplements and cognition outcomes in healthy populations across the lifespan; however, omega-3 dietary interventions are limited to studies in children and adolescents. Future studies should compare the effects of dietary omega-3 with omega-3 supplementation before further conclusions can be drawn.
... Another important constituent of dietary fats is polyunsaturated fatty acids, which can be further subdivided into omega-3 and omega-6 fatty acids. Many studies using a variety of models show that a decrease in omega-6/omega-3 ratio has anti-inflammatory effects (121)(122)(123)(124)(125). A study using mice reported that the omega-3-derived lipid mediator protectin D1, significantly reduced influenza virus replication (126). ...
... Many studies using a variety of models show that a decrease in omega-6/omega-3 ratio has anti-inflammatory effects (121)(122)(123)(124)(125). A study using mice reported that the omega-3-derived lipid mediator protectin D1, significantly reduced influenza virus replication (126). Moreover, a randomized controlled trial showed that omega-3 supplements were able to lower inflammation in healthy middle-aged and older adults (124). The data showed that administration of 1,25 and 2.5 g/d of omega-3 decreased the IL-6 serum level by 10 and 12%, respectively (124). ...
... Moreover, a randomized controlled trial showed that omega-3 supplements were able to lower inflammation in healthy middle-aged and older adults (124). The data showed that administration of 1,25 and 2.5 g/d of omega-3 decreased the IL-6 serum level by 10 and 12%, respectively (124). Another randomized control study showed that supplementation of omega 3 for 12 weeks reduced the production of IL-6, and lowered anxiety by 20%. ...
... Another important constituent of dietary fats is polyunsaturated fatty acids, which can be further subdivided into omega-3 and omega-6 fatty acids. Many studies using a variety of models show that a decrease in omega-6/omega-3 ratio has anti-inflammatory effects (121)(122)(123)(124)(125). A study using mice reported that the omega-3-derived lipid mediator protectin D1, significantly reduced influenza virus replication (126). ...
... Many studies using a variety of models show that a decrease in omega-6/omega-3 ratio has anti-inflammatory effects (121)(122)(123)(124)(125). A study using mice reported that the omega-3-derived lipid mediator protectin D1, significantly reduced influenza virus replication (126). Moreover, a randomized controlled trial showed that omega-3 supplements were able to lower inflammation in healthy middle-aged and older adults (124). The data showed that administration of 1,25 and 2.5 g/d of omega-3 decreased the IL-6 serum level by 10 and 12%, respectively (124). ...
... Moreover, a randomized controlled trial showed that omega-3 supplements were able to lower inflammation in healthy middle-aged and older adults (124). The data showed that administration of 1,25 and 2.5 g/d of omega-3 decreased the IL-6 serum level by 10 and 12%, respectively (124). Another randomized control study showed that supplementation of omega 3 for 12 weeks reduced the production of IL-6, and lowered anxiety by 20%. ...
Article
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The new coronavirus pandemic continues to spread causing further public health, social, and economic issues. The disparities in the rates of death between countries poses questions about the importance of lifestyle habits and the immune status of populations.An exploration of dietary habits and COVID-19-related death might unravel associations between these two variables. Indeed, while both nutritional excess and deficiency are associated with immunodeficiency, adequate nutrition leading to an optimally functioning immune system may be associated with better outcomes with regards to preventing infection and complications of COVID-19, as well as developing a better immune response to other pathogenic viruses and microorganisms. This article outlines the key functions of the immune system and how macronutrients, micronutrients, and metabolites from the gut microbiome can be essential in the development of an efficient immune system. In addition, the effects of intermittent fasting on the inflammatory state as well as metabolic parameters will be discussed.
... Of the 14 RCTs on DHA, 5 used DHA from algae (13,20,22,23,43), 4 from fish oil (10,14,42,45), 1 from enzyme synthesis (38), and the remaining trials did not report the source of DHA. Of the 11 RCTs on EPA, 7 used EPA from fish oil (10,14,21,36,39,40,44), 1 from yeast (13), and the remaining trials did not report the information. Of the 9 RCTs that reported the form of DHA and EPA, 6 used a triglyceride formulation (13,14,21,36,38,43), 2 provided the supplements in the form of ethyl esters (10,41), and 1 used DHA as monoglycerides (45). ...
... DHA, EPA, and inflammation 7 in 17 RCTs (85%) (10, 13, 14, 20-23, 35-41, 43, 44), TNF-α was investigated in 11 RCTs (47%) (10,13,14,22,23,(36)(37)(38)(39)(40)(41), and adiponectin was investigated in 2 RCTs (10%) (14,35). Subclinical inflammation was specified as the primary outcome in 6 trials (30%) (11,14,22,39,40,42). ...
... DHA, EPA, and inflammation 7 in 17 RCTs (85%) (10, 13, 14, 20-23, 35-41, 43, 44), TNF-α was investigated in 11 RCTs (47%) (10,13,14,22,23,(36)(37)(38)(39)(40)(41), and adiponectin was investigated in 2 RCTs (10%) (14,35). Subclinical inflammation was specified as the primary outcome in 6 trials (30%) (11,14,22,39,40,42). The majority of trials (85%) performed a per-protocol analysis of data; an intent-to-treat analysis of the results was used in only 3 trials (13,20,39). ...
Article
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Recent data from randomized clinical trials (RCTs) suggest that DHA may have stronger anti-inflammatory effects than EPA. This body of evidence has not yet been quantitatively reviewed. The aim of this study was to compare the effect of DHA and EPA on several markers of systemic inflammation by pairwise and network meta-analyses of RCTs. MEDLINE, EMBASE, and The Cochrane Library were searched through to September 2019. We included RCTs of ≥7 d on adults regardless of health status that directly compared the effects of DHA with EPA and RCTs of indirect comparisons, in which the effects of DHA or EPA were compared individually to a control fatty acid. Differences in circulating concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and adiponectin were the primary outcome measures. Data were pooled by pairwise and network meta-analysis and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic) in the pairwise meta-analysis. Inconsistency and transitivity were evaluated in the network meta-analysis. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Eligibility criteria were met by 5 RCTs (N = 411) for the pairwise meta-analysis and 20 RCTs (N = 1231) for the network meta-analysis. In the pairwise meta-analysis, DHA and EPA had similar effects on plasma CRP [MDDHA versus EPA = 0.14 mg/L (95% CI: -0.57, 0.85); I2 = 61%], IL-6 [MDDHA versus EPA = 0.10 pg/mL (-0.15, 0.34); I2 = 40%], and TNF-α [MDDHA versus EPA = -0.10 pg/mL (-0.37, 0.18); I2 = 40%]. In the network meta-analysis, the effects of DHA and EPA on plasma CRP [MDDHA versus EPA = -0.33 mg/L (-0.75, 0.10)], IL-6 [MDDHA versus EPA = 0.09 pg/mL (-0.12, 0.30)], and TNF-α [MDDHA versus EPA = -0.02 pg/mL (-0.25, 0.20)] were also similar. DHA and EPA had similar effects on plasma adiponectin in the network meta-analysis. Results from pairwise and network meta-analyses suggest that supplementation with either DHA or EPA does not differentially modify systemic markers of subclinical inflammation.
... Prior publications from this randomized, placebo-controlled trial (RCT) showed that 4 months of omega-3 supplementation lowered basal inflammation and oxidative stress [2,14], but this preplanned ancillary substudy investigated whether it altered the stress responsivity of biomarkers relevant to telomere length and cellular aging (i.e., cortisol, inflammatory cytokines, and telomerase). Cortisol and pro-inflammatory cytokines naturally rise after acute stress, but exaggerated cortisol responses are associated with shorter telomeres both cross-sectionally and longitudinally [15,16], and proinflammatory cytokines fuel oxidative stress [17,18], which shortens telomeres [19]. ...
... Each participant provided written informed consent. These ancillary hypotheses were prespecified and are distinct from the primary results [2,14]. ...
... Due to our desire to study sedentary, overweight individuals, only those who engaged in <2 h of vigorous physical activity per week and had a body mass index (BMI) between 22.5 and 50 were included. The parent study's exclusionary criteria, described elsewhere, yielded a sample that was free of metabolic, autoimmune, and inflammatory diseases and did not take medications that alter mood, cardiovascular, or immune function [2,14]. ...
Article
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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.
... Another important constituent of dietary fats is polyunsaturated fatty acids, which can be further subdivided into omega-3 and omega-6 fatty acids. Many studies using a variety of models show that a decrease in omega-6/omega-3 ratio has anti-inflammatory effects (121)(122)(123)(124)(125). A study using mice reported that the omega-3-derived lipid mediator protectin D1, significantly reduced influenza virus replication (126). ...
... Many studies using a variety of models show that a decrease in omega-6/omega-3 ratio has anti-inflammatory effects (121)(122)(123)(124)(125). A study using mice reported that the omega-3-derived lipid mediator protectin D1, significantly reduced influenza virus replication (126). Moreover, a randomized controlled trial showed that omega-3 supplements were able to lower inflammation in healthy middle-aged and older adults (124). The data showed that administration of 1,25 and 2.5 g/d of omega-3 decreased the IL-6 serum level by 10 and 12%, respectively (124). ...
... Moreover, a randomized controlled trial showed that omega-3 supplements were able to lower inflammation in healthy middle-aged and older adults (124). The data showed that administration of 1,25 and 2.5 g/d of omega-3 decreased the IL-6 serum level by 10 and 12%, respectively (124). Another randomized control study showed that supplementation of omega 3 for 12 weeks reduced the production of IL-6, and lowered anxiety by 20%. ...
Article
Full-text available
The new coronavirus pandemic continues to spread causing further public health, social, and economic issues. The disparities in the rates of death between countries poses questions about the importance of lifestyle habits and the immune status of populations. An exploration of dietary habits and COVID-19-related death might unravel associations between these two variables. Indeed, while both nutritional excess and deficiency are associated with immunodeficiency, adequate nutrition leading to an optimally functioning immune system may be associated with better outcomes with regards to preventing infection and complications of COVID-19, as well as developing a better immune response to other pathogenic viruses and microorganisms. This article outlines the key functions of the immune system and how macronutrients, micronutrients, and metabolites from the gut microbiome can be essential in the development of an efficient immune system. In addition, the effects of intermittent fasting on the inflammatory state as well as metabolic parameters will be discussed.
... Maki et al. [78]reported that supplementation of krill oil (216 mg EPA, 90 mg DHA), menhaden oil (212 mg DHA, 178 mg EPA) or control (2 g olive oil) for 4-week to 25 overweight individuals did not alter plasma CRP. In contrary, Kiecolt-Glaser et al. (2012) reported that the consumption of two doses of n-3 PUFA (1.25 vs 2.5 g/day, EPA: DHA ratio is 7:1) for 4 months in 46 abdominally overweight individuals resulted in discernable reduction in plasma TNF-α and IL-6 concentrations [79]. It is plausible that the longer duration with sufficiently powered design enable the detection of positive findings. ...
... Furthermore, ideal balance of EPA to DHA may play a critical role as evidence suggests that EPA may be more anti-inflammatory than DHA [80,81]. In agreement with Kiecolt-Glaser et al. [79], a recent study found that 55 severely obese nondiabetic patients provided with 3.36 g n-3 PUFA (EPA, DHA) for 8-week experienced a marked decrease in plasma IL-6 but not hsCRP concentrations [82]. Interestingly, the study also reported that n-3 PUFA decreased the expression of varying inflammatory genes in subcutaneous adipose tissue and increased the production of eicosanoids in both visceral and subcutaneous adipose tissue compared with butter fat (control). ...
Article
The increasing incidence rate of breast cancer in the last few decades is known to be linked to the upward trend of obesity prevalence worldwide. The consumption of high-fat diet in particular has been correlated with postmenopausal breast cancer risk. The underlying mechanisms, using suitable and reliable experimental mouse model, however, is lacking. The current review aims to discuss the evidence available from mouse models on the effects of dietary fats intake on postmenopausal breast cancer. We will further discuss the biochemical mechanisms involved in the occurrence of postmenopausal breast cancer. In addition, the methodological considerations and their limitations in obesity-related postmenopausal breast cancer, such as choice of mouse models and breast cancer cell lines as well as the study duration will be reviewed. The current review will provide a platform for further development of new xenograft models which may offer the opportunity to investigate the mechanisms of postmenopausal breast cancer in a greater detail.
... The main contributors to the growing worldwide incidence of low omega-3 status are a low intake of fish and high intake of vegetable oils that are high in linoleic acid, which displaces omega-3 fatty acids in cell membrane phospholipids 140,141 . In turn, various RCTs have shown that omega-3 fatty acid supplementation reduces inflammation [142][143][144] and may thus have health-promoting effects [141][142][143][144] . ...
... The main contributors to the growing worldwide incidence of low omega-3 status are a low intake of fish and high intake of vegetable oils that are high in linoleic acid, which displaces omega-3 fatty acids in cell membrane phospholipids 140,141 . In turn, various RCTs have shown that omega-3 fatty acid supplementation reduces inflammation [142][143][144] and may thus have health-promoting effects [141][142][143][144] . ...
Article
Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI. Systemic chronic inflammation increases with age and is linked to the development of several diseases, as presented in this Perspective.
... Therefore, it is recommended to consume EPA and DHA through the diet. DHA plays an important role in the function and responsiveness of cell membranes, tissue metabolism and hormonal and other signaling pathways [4,5]. It also constitutes the major fatty acid in the brain and retina [6]. ...
... Two different pathways exist for PUFA synthesis: the oxygen-dependent aerobic fatty acid synthase pathway (FAS), also known as elongase-desaturase pathway, and the oxygen-independent anerobic polyketide synthase pathway (PKS)-also designated as the PUFA synthase pathway [45]. In the FAS pathway, the starting point for PUFA synthesis is C18:3-9,12,15, which is converted by ∆6 desaturase into C18:4-6,9,12,15 and by elongase into C20: [4][5][6][7][8]11,14,17. The latter is then converted into C20: 8,11,14,17 by ∆5 desaturase, followed by elongation to 22:5-7,10,13,16,19 and, finally, conversion into DHA (22:6-4,7,10,13,16,19) by ∆4 desaturase [43,[45][46][47]. ...
Article
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Thraustochytrids are considered natural producers of omega-3 fatty acids as they can synthesize up to 70% docosahexaenoic acids (DHA) of total lipids. However, commercial and sustainable production of microbial DHA is limited by elevated cost of carbon substrates for thraustochytrids cultivation. This problem can be addressed by utilizing low-cost renewable substrates. In the present study, growth, lipid accumulation and fatty acid profiles of the marine thraustochytrid Aurantiochytrium sp. T66 (ATCC-PRA-276) cultivated on volatile fatty acids (C1, formic acid; C2, acetic acid; C3, propionic acid; C4, butyric acid; C5, valeric acid and C6, caproic acid) and glucose as control were evaluated for the first time. This strain showed an inability to utilize C3, C5 and C6 as a substrate when provided at >2 g/L, while efficiently utilizing C2 and C4 up to 40 g/L. The highest cell dry weight (12.35 g/L) and total lipid concentration (6.59 g/L) were attained when this strain was cultivated on 40 g/L of butyric acid, followed by cultivation on glucose (11.87 g/L and 5.34 g/L, respectively) and acetic acid (8.70 g/L and 3.43 g/L, respectively). With 40 g/L butyric acid, the maximum docosahexaenoic acid content was 2.81 g/L, corresponding to 42.63% w/w of total lipids and a yield of 0.23 g/gcell dry weight (CDW). This marine oleaginous microorganism showed an elevated potential for polyunsaturated fatty acids production at higher acetic and butyric acid concentrations than previously reported. Moreover, fluorescence microscopy revealed that growth on butyric acid caused cell size to increase to 45 µm, one of the largest values reported for oleaginous microorganisms, as well as the presence of numerous tiny lipid droplets.
... Although fatty acid composition may vary due to conditions such as different habitats, species, and cultivation conditions, the caviar contained high levels of PUFAs, especially DHA and EPA, which are the main components of phospholipids [24][25][26][27][28][29]. Several studies have demonstrated that the dietary intake of PUFAs showed a therapeutic efficacy to prevent and inhibit inflammatory and cardiovascular diseases as well as atopic dermatitislike skin disease [19,[30][31][32]. Recently, a number of studies have reported that compounds derived ...
... Although fatty acid composition may vary due to conditions such as different habitats, species, and cultivation conditions, the caviar contained high levels of PUFAs, especially DHA and EPA, which are the main components of phospholipids [24][25][26][27][28][29]. Several studies have demonstrated that the dietary intake of PUFAs showed a therapeutic efficacy to prevent and inhibit inflammatory and cardiovascular diseases as well as atopic dermatitis-like skin disease [19,[30][31][32]. Recently, a number of studies have reported that compounds derived from marine organisms exhibit skin anti-aging activities. ...
Article
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In this study, caviar (sturgeon eggs) was used to elucidate its roles in adiponectin production and skin anti-aging. Recently, caviar has been largely used not only as a nutritional food, but also in cosmetic products. In particular, it has been reported that docosahexaenoic acid (DHA), as one of the main phospholipid components of caviar extract, induces intracellular lipid accumulation and the expression of adiponectin in adipocytes. Although adipocytes are well known to be associated with the skin dermis by secreting various factors (e.g., adiponectin), the effects of caviar extract and DHA on the skin are not well studied. Here, we demonstrate the effects of caviar extract and DHA on adipocyte differentiation and adiponectin production, resulting in a preventive role in UV-irradiated skin aging. Caviar extract and DHA enhanced adipocyte differentiation and promoted the synthesis of transcription factors controlling adipocyte differentiation and adiponectin. In addition, the mRNA expression levels of matrix metalloproteinase-1 (MMP-1) were decreased in UVB-irradiated Hs68 fibroblasts that were cultured in conditioned medium from caviar extract or DHA-treated differentiated adipocytes. Taken together, these results indicate that caviar extract and DHA induce adipocyte differentiation and adiponectin production, thereby inhibiting UVB-induced premature skin aging via the suppression of MMP-1 production.
... However, the incidence was quite lower in a modular diet enriched with the omega-3 fatty acid group. Since omega-3 fatty acids have potential anti-inflammatory actions by reducing immune responses, their benefits of immunomodulation have been explored in previous studies [33][34][35]. Considering the effects of omega-3 fatty acids on infection rates, it was shown that patients receiving omega-3 parenteral nutrition had a low risk of nosocomial infections [36]. In a previous study, clinical benefits such as lower rates of sepsis and GI complications due to a well-tolerated omega-3-fatty-acid-containing diet were well noted [21]. ...
Article
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Background: In burn patients, the profound effect of nutritional support on improved wound healing and a reduced rate of hospitalization and mortality has been documented. Fish oil as a primary source of omega-3 fatty acids in nutritional support may attenuate the inflammatory response and enhance immune function; however, unclear effects on the improvement of clinical outcomes in burn patients remain. Methods: The systematic literature review was conducted by searching the electronic databases: Cochrane Library, PubMed, ScienceDirect, and Scopus to assess the randomized controlled trials of nutritional support with omega-3 fatty acids compared to control diets in patients that presented with burns from any causes. Results: Seven trials were included in this meta-analysis. We found no significant differences in length of stay (LOS) (p = 0.59), mortality (p = 0.86), ventilation days (p = 0.16), gastrointestinal complications-e.g., constipation and diarrhea (p = 0.73)-or infectious complications-e.g., pneumonia and sepsis (p = 0.22)-between the omega-3-fatty-acid-receiving group and the control/other diets group. Conclusions: We did not find a benefit of omega-3 support in reducing the various complications, mortality and LOS in burn patients. Further studies are necessary to find the effect of nutritional support with omega-3 fatty acids over low-fat diets in this population.
... According to Rangel-Huerta's meta-analysis, consumption of 900 mg-2000 mg n-3 PUFAs does not change inflammatory biomarkers in healthy subjects (Rangel-Huerta et al., 2012). On the other hand, doses between 1250 and 2400 mg n-3 PUFA for 4 months lowered inflammation in sedentary and overweight middle-aged and older adults (Kiecolt-Glaser et al., 2012). Lp-PLA2, another anti-inflammatory marker was significantly reduced by a high dose of EPA (1800 mg) but not by DHA (Asztalos et al., 2016). ...
Article
Prevention and treatment of non-communicable diseases (NCDs), including cardiovascular disease, diabetes, obesity, cancer, Alzheimer’s and Parkinson’s disease, arthritis, non-alcoholic fatty liver disease and various infectious diseases; lately most notably COVID-19 have been in the front line of research worldwide. Although targeting different organs, these pathologies have common biochemical impairments – redox disparity and, prominently, dysregulation of the inflammatory pathways. Research data have shown that diet components like polyphenols, poly-unsaturated fatty acids (PUFAs), fibres as well as lifestyle (fasting, physical exercise) are important factors influencing signalling pathways with a significant potential to improve metabolic homeostasis and immune cells’ functions. In the present manuscript we have reviewed scientific data from recent publications regarding the beneficial cellular and molecular effects induced by dietary plant products, mainly polyphenolic compounds and PUFAs, and summarize the clinical outcomes expected from these types of interventions, in a search for effective long-term approaches to improve the immune system response.
... Responses following 4-month supplementation of omega-3 fatty acids of 2.5 g/d and 1.25 g/d vs. placebo were compared in a randomized controlled trial (RCT) study in healthy adults. A significant decrease in serum IL-6 by 10% and 12% in the low and high dose omega-3 FAs groups, respectively, was seen, compared to a 36% increase in the placebo group [143]. Likewise, another RCT reported that omega-3 FA supplementation resulted in reduced IL-6 production, while decreasing omega-6/omega-3 ratios reduced the production of stimulated IL-6 and TNF-α [144]. ...
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The coronavirus-disease 2019 (COVID-19) was announced as a global pandemic by the World Health Organization. Challenges arise concerning how to optimally support the immune system in the general population, especially under self-confinement. An optimal immune response depends on an adequate diet and nutrition in order to keep infection at bay. For example, sufficient protein intake is crucial for optimal antibody production. Low micronutrient status, such as of vitamin A or zinc, has been associated with increased infection risk. Frequently, poor nutrient status is associated with inflammation and oxidative stress, which in turn can impact the immune system. Dietary constituents with especially high anti-inflammatory and antioxidant capacity include vitamin C, vitamin E, and phytochemicals such as carotenoids and polyphenols. Several of these can interact with transcription factors such as NF-kB and Nrf-2, related to anti-inflammatory and antioxidant effects, respectively. Vitamin D in particular may perturb viral cellular infection via interacting with cell entry receptors (angiotensin converting enzyme 2), ACE2. Dietary fiber, fermented by the gut microbiota into short-chain fatty acids, has also been shown to produce anti-inflammatory effects. In this review, we highlight the importance of an optimal status of relevant nutrients to effectively reduce inflammation and oxidative stress, thereby strengthening the immune system during the COVID-19 crisis.
... Based on the results of a randomized, controlled study published in 2018, high-dose (1.5 g/day EPA and 1.0 g/day DHA) n-3 supplementation can reduce plasma levels of both IL-6 and IL-1ß (Tan et al., 2018). The anti-inflammatory effect of EPA and DHA supplementation seems consistent with most of the previous clinical findings (Fritsche, 2006;Vedin et al., 2008;Kiecolt-Glaser et al., 2012;Muldoon et al., 2016;Calder et al., 2020) (Table 1). ...
... [54][55][56][57][58] A healthy dietary pattern is anti-inflammatory and may contribute to the upregulation of brain-derived neurotropic factor levels because of higher intakes of long-chain n-3 polyunsaturated fatty acids, vitamin C, folate, polyphenols, phytochemicals, and dietary fibers. [59][60][61][62] Therefore, a healthy dietary pattern may contribute to a reduction of depression risk. Moreover, neurologic damage such as a dysfunction of the hypothalamus-pituitary-adrenal axis is a risk factor for depression. ...
Article
Context Diet may be one of the modifiable environmental factors that could reduce depressive symptoms or abate the development of depression without side effects. However, previous reviews mainly focused on general adult populations. Objective The aim of this systematic review and meta-analysis was to explore the association between healthy dietary patterns and depression risk in older adults. Data Sources Eight databases were searched up to September 2019. The inclusion criteria were older adults aged ≥ 65 years, healthy dietary patterns, depression assessed by a physician or by validated screening tools, and quantitative study design. Data Extraction Data were extracted independently by 2 researchers, and the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Data Analysis Meta-analysis was conducted by calculating the pooled odds ratio (OR) and 95% CIs. A total of 18 eligible studies were meta-analyzed. Results showed that a healthy dietary pattern is associated with a reduced risk of depression in older adults (OR, 0.85; 95%CI, 0.78–0.92; P < 0.001). There was high heterogeneity (I2 = 64.9%; P < 0.001) among the studies. Subgroup analyses indicated that sample size and depression screening tools were the main sources of study heterogeneity. Conclusions An inverse association between healthy dietary patterns and depression risk in older adults was found. However, the high heterogeneity among the studies should be considered. Systematic Review Registration PROSPERO registration no. CRD 42020169195.
... The long-chain PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be converted from α-linolenic acid, but the reaction occurs at low rates, thus requiring their intake through the diet (Chiu et al., 2008). DHA acts as an anti-inflammatory agent and constitutes a major structural component of the cell membrane (Kiecolt-Glaser et al., 2012). It usually accumulates in the brain grey matter and retinal tissues, making it important for early visual and neurological development (Lazzarin et al., 2009). ...
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The commercial production of docosahexaenoic acid (DHA) from oleaginous microorganisms is getting more attention due to several advantages over fish oils. The processing cost became a major bottleneck for commercialization of DHA from microorganisms. The most of cost shares in the feedstock to cultivate the microorganisms and downstream processing. The cost of feedstock can be compensated with the utilization of substrate from waste stream whereas production of value-added chemicals boosts the economic viability of nutraceutical production. In the present study, the docosahexaenoic acid (DHA)-producing marine protist Aurantiochytrium sp. T66 was cultivated on post-consumption food waste hydrolysate for the mining of squalene. After 120 h of cultivation, cell dry weight was 14.7 g/L, of which 6.34 g/L (43.13%; w/w) were lipids. DHA accounted for 2.15 g/L (34.05%) of total extracted lipids or 0.15 g/gCDW. Maximum squalene concentration and yield were 1.05 g/L and 69.31 mg/gCDW, respectively. Hence, utilization of food waste represents an excellent low-cost strategy for cultivating marine oleaginous thraustochytrids and produce squalene as a byproduct of DHA.
... For details, see the text. Immunomodulatory properties of dietary FAs during systemic inflammation have been investigated in both healthy and diseased people [14][15][16][17][18][19][20]. The increased consumption of SFAs from processed foods is associated with an increased risk of atherosclerosis, coronary heart disease, obesity, and metabolic syndrome, which has been extensively reviewed elsewhere [21][22][23][24]. ...
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Diet-derived fatty acids (FAs) are essential sources of energy and fundamental structural components of cells. They also play important roles in the modulation of immune responses in health and disease. Saturated and unsaturated FAs influence the effector and regulatory functions of innate and adaptive immune cells by changing membrane composition and fluidity and by acting through specific receptors. Impaired balance of saturated/unsaturated FAs, as well as n-6/n-3 polyunsaturated FAs has significant consequences on immune system homeostasis, contributing to the development of many allergic, autoimmune, and metabolic diseases. In this paper, we discuss up-to-date knowledge and the clinical relevance of the influence of dietary FAs on the biology, homeostasis, and functions of epithelial cells, macrophages, dendritic cells, neutrophils, innate lymphoid cells, T cells and B cells. Additionally, we review the effects of dietary FAs on the pathogenesis of many diseases, including asthma, allergic rhinitis, food allergy, atopic dermatitis, rheumatoid arthritis, multiple sclerosis as well as type 1 and 2 diabetes.
... Numerous clinical studies have focused mainly on the anti-inflammatory properties of ω3 PUFAs as well as on their neuroprotective and regenerative effects. [71][72][73][74] In particular, one review analysed human brain MRI studies and experimental studies and confirmed that ω3 PUFAs can protect the brain during ageing by preventing peroxidation, inflammation and excitotoxicity; modulating neurotransmission; and increasing neurogenesis, thereby improving the brain's 'coping' mechanisms during ageing. 75 We have established here that ω3 PUFAs have protective and therapeutic potential against age-related decline in visual function in 2-year-old-aged C57BL/6J mice. ...
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Objective To evaluate the therapeutic effects of omega-3 (ω3) fatty acids in the retina of aged mice when the blood arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio is maintained between 1.0 and 1.5. Methods and analysis Aged (24-month-old) wild-type C57BL/6J mice were allocated to two groups: ω3 treated and untreated. Treatment with ω3 was by daily gavage administration of EPA and docosahexaenoic acid for 60 days. Gas chromatography was used to identify and quantify fatty acids in the blood and retina. To count lipofuscin granules and measure the photoreceptor layer, eyecups were examined histologically using transmission electron microscopy and light microscopy. We also analysed eyecups using mass spectrometry-based proteomics. Results AA levels were lower, and EPA levels were higher, in the blood and retinas of the ω3-treated group than in the untreated group, resulting in a lower AA/EPA ratio. The ω3-treated group also showed significantly fewer lipofuscin granules and a thicker outer nuclear layer than the untreated group. Proteomic analysis revealed significantly greater expression of myelin basic protein, myelin regulatory factor-like protein, myelin proteolipid protein and glial fibrillar acidic protein in the ω3-treated group than in the untreated group. Three different pathways were significantly affected by ω3 treatment: fatty acid elongation, biosynthesis of unsaturated fatty acids and metabolic pathways. Conclusion Two months of ω3 supplementation (when the blood AA/EPA~1.0–1.5) in aged mice reduced lipofuscin granule formation in the retina and protected the photoreceptor layer, suggesting that ω3 supplementation slows normal age-related retinal degeneration.
... The Multicenter Osteoarthritis Study in 2012, an observational study of Omega-3 and Omega-6 plasma levels, found that knee patellofemoral cartilage loss was inversely associated with Omega-3 plasma levels [28]. Daily dosing of 2700 mg of Omega-3 PUFAs is suggested for anti-inflammatory effect noting benefits may be delayed up to 3-4 months [29,30]. Some commercially sold single-serving mackerel cans are advertised to contain 3500 mg of Omega-3 PUFA per serving whereas fish oil supplements have widely varying components and dosages and often unknown amounts of toxic heavy metals such as mercury. ...
... Indeed, fish oil supplementation decreases pro-inflammatory cytokine expression, such as IL-1β in blood monocytes, and improves the symptoms of patients suffering from rheumatoid arthritis (Kremer et al., 1990;James et al., 1997;Kremer, 2000) or multiple sclerosis (Stewart and Bowling, 2005;Weinstock-Guttman et al., 2005). Moreover, DHA supply significantly decreases the circulating inflammatory markers and the oxidative stress (Freund-Levi et al., 2006;Kiecolt-Glaser et al., 2012). DHA supply for several months also improves the working and long-term memories in patients with moderate cognitive alterations (Freund-Levi et al., 2006;Lee et al., 2013). ...
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In the past few decades, as a result of their anti-inflammatory properties, n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFAs), have gained greater importance in the regulation of inflammation, especially in the central nervous system (in this case known as neuroinflammation). If sustained, neuroinflammation is a common denominator of neurological disorders, including Alzheimer’s disease and major depression, and of aging. Hence, limiting neuroinflammation is a real strategy for neuroinflammatory disease therapy and treatment. Recent data show that n-3 LC-PUFAs exert anti-inflammatory properties in part through the synthesis of specialized pro-resolving mediators (SPMs) such as resolvins, maresins and protectins. These SPMs are crucially involved in the resolution of inflammation. They could be good candidates to resolve brain inflammation and to contribute to neuroprotective functions and could lead to novel therapeutics for brain inflammatory diseases. This review presents an overview 1) of brain n-3 LC-PUFAs as precursors of SPMs with an emphasis on the effect of n-3 PUFAs on neuroinflammation, 2) of the formation and action of SPMs in the brain and their biological roles, and the possible regulation of their synthesis by environmental factors such as inflammation and nutrition and, in particular, PUFA consumption.
... The current sample included 105 healthy, sedentary adults ages 40-85 years who provided data as part of a parent trial investigating the effect of omega-3 supplementation on inflammation and depression (Kiecolt-Glaser et al., 2012). Analyses utilized data from the trial's baseline visit, before supplementation. ...
Article
The Western diet, characterized by high intake of saturated fat, sugar, and salt, is associated with elevated inflammation and chronic disease risk. Few studies have investigated molecular mechanisms linking diet and inflammation; however, a small number of randomized controlled trials suggest that consuming an anti-inflammatory diet (i.e., a primarily plant-based diet rich in monounsaturated fat and lean protein) decreases proinflammatory gene expression. The current study investigated the association between everyday diet and proinflammatory gene expression, as well as the extent to which central adiposity and social involvement modulate risk. Participants were healthy middle-aged and older adults (N = 105) who completed a food frequency questionnaire and reported how many close social roles they have. Anthropometric measurements and blood samples also were collected; gene expression data were analyzed from LPS-stimulated peripheral blood mononuclear cells for interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. The inflammatory potential of each participant's diet was calculated using the Dietary Inflammatory Index (DII®). Participants with higher DII® scores, indicating a more proinflammatory diet, had greater IL-6 (b = -0.02, SE = 0.008, p = .01), IL-1β (b = -0.01, SE = 0.006, p = .03), and TNF-α (b = -0.01, SE = 0.005, p = .04) gene expression if they had a smaller sagittal abdominal diameter (SAD); effects were not seen among those with higher SADs. Social involvement served a protective role, such that participants with smaller SADs had greater IL-6 (b = 0.01, SE = 0.004, p = .049) and IL-1β (b = 0.01, SE = 0.003, p = .045) gene expression only if they had less social involvement; there was no effect of diet on gene expression among those who reported greater social participation. Results are the first to demonstrate a link between self-reported diet and proinflammatory gene expression. Importantly, the effect of diet on gene expression depended upon both body fat composition and social participation, both of which have previously been linked directly with proinflammatory gene expression and inflammation.
... While there is no direct clinical evidence related to the use of n-3 PUFAs in COVID-19 patients, the application of n-3 PUFAs in several inflammatory settings, including cardiovascular disorders, has been demonstrated to ameliorate detrimental immune reactions by several mechanisms (Rogero et al., 2020). The anti-inflammatory effect of n-3 PUFAs seems to be consistent across several previous clinical findings (Calder, Carr, Gombart, & Eggersdorfer, 2020;Fritsche, 2006;Kiecolt-Glaser et al., 2012;Vedin et al., 2008). Intriguingly, Tan et al. recently demonstrated in a randomized controlled study that high-dose n-3 PUFA supplementation (1.5 g/day EPA and 1.0 g/day DHA) markedly reduces plasma levels of IL-6, IL-1β and TNF-α after 4 weeks of therapy in middle or late-aged patients with chronic venous leg ulcers suggesting n-3 PUFAs as an effective low-risk dietary intervention to modulate inflammation (Tan, Sullenbarger, Prakash, & McDaniel, 2018). ...
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Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has currently led to a global pandemic with millions of confirmed and increasing cases around the world. The novel SARS-CoV-2 not only affects the lungs causing severe acute respiratory dysfunction but also leads to significant dysfunction in multiple organs and physiological systems including the cardiovascular system. A plethora of studies have shown the viral infection triggers an exaggerated immune response, hypercoagulation and oxidative stress, which contribute significantly to poor cardiovascular outcomes observed in COVID-19 patients. To date, there are no approved vaccines or therapies for COVID-19. Accordingly, cardiovascular protective and supportive therapies are urgent and necessary to the overall prognosis of COVID-19 patients. Accumulating literature has demonstrated the beneficial effects of n-3 polyunsaturated fatty acids (n-3 PUFA) toward the cardiovascular system, which include ameliorating uncontrolled inflammatory reactions, reduced oxidative stress and mitigating coagulopathy. Moreover, it has been demonstrated the n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors to a group of potent bioactive lipid mediators, generated endogenously, which mediate many of the beneficial effects attributed to their parent compounds. Considering the favorable safety profile for n-3 PUFAs and their metabolites, it is reasonable to consider n-3 PUFAs as potential adjuvant therapies for the clinical management of COVID-19 patients. In this article, we provide an overview of the pathogenesis of cardiovascular complications secondary to COVID-19 and focus on the mechanisms that may contribute to the likely benefits of n-3 PUFAs and their metabolites.
... Ω-3 polyunsaturated fatty acids (PUFAs) are an interesting alternative, given their antiinflammatory and anabolic mechanisms of action (13). Ω-3 supplementation was shown to lower systemic levels of pro-inflammatory cytokines in overweight (14) and obese (15) adults, Downloaded from https://academic.oup.com/biomedgerontology/advance-article/doi/10.1093/gerona/glaa309/6025407 by KU Leuven Libraries user on 08 December 2020 and in patient populations (16), but not consistently in (middle-)aged adults (50-95yr) (17)(18)(19). ...
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Old skeletal muscle exhibits decreased anabolic sensitivity, eventually contributing to muscle wasting. Besides anabolism, also muscle inflammation and catabolism are critical players in regulating the old skeletal muscle's sensitivity. Omega-3 fatty acids (ω-3) are an interesting candidate to reverse anabolic insensitivity via anabolic actions. Yet, it remains unknown whether ω-3 also attenuates muscle inflammation and catabolism. The present study investigates the effect of ω-3 supplementation on muscle inflammation and metabolism (anabolism/catabolism) upon resistance exercise (RE). Twenty-three older adults (OA) (65-84yr;8♀) were randomized to receive ω-3 (~3g·d-1) or corn oil (PLAC) and engaged in a 12-wk RE program (3x·wk-1). Before and after intervention, muscle volume, strength and systemic inflammation were assessed, and muscle biopsies were analysed for markers of anabolism, catabolism and inflammation. Isometric knee-extensor strength increased in ω-3 (+12.2%), but not in PLAC (-1.4%; p interaction =0.015), whereas leg press strength improved in both conditions (+27.1%; p time <0.001). RE, but not ω-3, decreased inflammatory (p65NF-κB) and catabolic (FOXO1, LC3b) markers, and improved muscle quality. Yet, muscle volume remained unaffected by RE and ω-3. Accordingly, muscle anabolism (mTORC1) and plasma CRP remained unchanged by RE and ω-3, whereas serum IL-6 tended to decrease in ω-3 (p interaction =0.07). These results show that, despite no changes in muscle volume, RE-induced gains in isometric strength can be further enhanced by ω-3. However, ω-3 did not improve RE-induced beneficial catabolic or inflammatory adaptations. Irrespective of muscle volume, gains in strength (primary criterion for sarcopenia) might be explained by changes in muscle quality due to muscle inflammatory or catabolic signaling.
... Ω-3 polyunsaturated fatty acids (PUFAs) are an interesting alternative, given their antiinflammatory and anabolic mechanisms of action (13). Ω-3 supplementation was shown to lower systemic levels of pro-inflammatory cytokines in overweight (14) and obese (15) adults, and in patient populations (16), but not consistently in (middle-)aged adults (50-95yr) (17)(18)(19). ...
Article
Full-text available
Old skeletal muscle exhibits decreased anabolic sensitivity, eventually contributing to muscle wasting. Besides anabolism, also muscle inflammation and catabolism are critical players in regulating the old skeletal muscle’s sensitivity. Omega-3 fatty acids (ω-3) are an interesting candidate to reverse anabolic insensitivity via anabolic actions. Yet, it remains unknown whether ω-3 also attenuates muscle inflammation and catabolism. The present study investigates the effect of ω-3 supplementation on muscle inflammation and metabolism (anabolism/catabolism) upon resistance exercise (RE). Twenty-three older adults (OA) (65-84yr;8♀) were randomized to receive ω-3 (~3g·d -1) or corn oil (PLAC) and engaged in a 12-wk RE program (3x·wk -1). Before and after intervention, muscle volume, strength and systemic inflammation were assessed, and muscle biopsies were analysed for markers of anabolism, catabolism and inflammation. Isometric knee-extensor strength increased in ω-3 (+12.2%), but not in PLAC (-1.4%; pinteraction=0.015), whereas leg press strength improved in both conditions (+27.1%; ptime<0.001). RE, but not ω-3, decreased inflammatory (p65NF-κB) and catabolic (FOXO1, LC3b) markers, and improved muscle quality. Yet, muscle volume remained unaffected by RE and ω-3. Accordingly, muscle anabolism (mTORC1) and plasma CRP remained unchanged by RE and ω-3, whereas serum IL-6 tended to decrease in ω-3 (pinteraction=0.07). These results show that, despite no changes in muscle volume, RE-induced gains in isometric strength can be further enhanced by ω-3. However, ω-3 did not improve RE-induced beneficial catabolic or inflammatory adaptations. Irrespective of muscle volume, gains in strength (primary criterion for sarcopenia) might be explained by changes in muscle quality due to muscle inflammatory or catabolic signaling.
... Major depressive disorders (MDD) Depressive episodes in bipolar affective disorders [60][61][62][63][64][65][66][67] Depression during or post pregnancy [68][69][70] Depression in non-MDD mood disorders (e.g., premenstrual syndrome, dysthymia) [31,45,49,[71][72][73] Depression in other psychiatric conditions (e.g., borderline personality, self-harm, OCD) [74][75][76][77][78] Depression in established schizophrenia [79][80][81] Depression in Alzheimer's dementia/mild cognitive impairment [46,82,83] Depression in Parkinson's disease [84] Depression in medical conditions (cerebrovascular and metabolic diseases or cancer) [85][86][87][88][89] Depressive features in healthy individuals [90][91][92][93][94][95][96] Abbreviations: RCT: randomized controlled trial; OCD: obsessive-compulsive disorder. ...
Article
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Major depressive disorders (MDDs) are often associated with a deficiency in long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), as well as signs of low-grade inflammation. Epidemiological and dietary studies suggest that a high intake of fish, the major source of ω-3 PUFAs, is associated with lower rates of MDDs. Meta-analyses of randomized placebo-controlled ω-3 PUFAs intervention-trials suggest that primarily eicosapentaenoic acid (EPA), but not docosahexaenoic acid (DHA), is responsible for the proposed antidepressant effect. In this review, we dissect the current biological knowledge on EPA and DHA and their bioactive lipid metabolites to search for a pharmacological explanation of this, to date, unexplained clinical observation. Through enzymatic conversion by cyclooxygenase (COX), lipoxygenase (ALOX), and cytochrome P-450 monooxygenase (CYP), EPA and DHA are metabolized to major anti-inflammatory and pro-resolving lipid mediators. In addition, both ω-3 PUFAs are precursors for endocannabinoids, with known effects on immunomodulation, neuroinflammation, food intake and mood. Finally, both ω-3 PUFAs are crucial for the structure and organization of membranes and lipid rafts. While most biological effects are shared by these two ω-3 PUFAs, some distinct features could be identified: (1) The preferential CYP monooxygenase pathway for EPA and EPA derived eicosanoids; (2) The high CB2 receptor affinities of EPA-derived EPEA and its epoxy-metabolite 17,18-EEQ-EA, while the DHA-derived endocannabinoids lack such receptor affinities; (3) The competition of EPA but not DHA with arachidonic acid (AA) for particular glycerophospholipids. EPA and AA are preferentially incorporated into phosphatidylinositols, while DHA is mainly incorporated into phosphatidyl-ethanolamine, -serine and -choline. We propose that these distinct features may explain the superior antidepressant activity of EPA rich ω-3 PUFAs and that these are potential novel targets for future antidepressant drugs
... Omega-3 supplementation increases the EPA+DHA content of neutrophil membranes in vivo and inhibits the 5-lipoxygenase pathway and leukotriene B 4 -mediated functions of neutrophils in vitro [38]. Omega-3 supplementation significantly increased plasma EPA+DHA levels (50-100%) and decreased concentrations of IL-6 (10-12% vs 36% increase in placebo group) and TNFα (0.2 to − 2.3% vs 12% increase in placebo group) in healthy, middle-aged and older individuals [74]. Meta-analyses have confirmed this effect [72]. ...
Article
The neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and measures innate-adaptive immune system balance. The omega-3-index (O3I) measures the amount of EPA+DHA in blood. Both a low O3I and an elevated NLR are associated with increased risk for chronic disease and mortality, including cardiovascular diseases and cancer. Hypothesizing that low O3I may partly contribute to systemic chronic inflammation, we asked if a relationship existed between O3I and NLR in healthy adults (≥18y, n=28,871, 51% female) without inflammation [C-reactive protein (CRP) <3mg/mL)] who underwent a routine clinical assessment. NLR was inversely associated with O3I before (p<0.0001) and after adjusting for age, sex, BMI, and CRP (p<0.0001). Pearson correlations of other variables with NLR were r=0.06 (CRP), r=0.14 (age), and r=0.01(BMI). In this healthy population, an O3I <6.6% was associated with increasing NLR whereas NLR remained relatively constant (low) when O3I >6.6%, suggestive of a quiescent, balanced immune system.
... In a placebo-controlled randomized trial, a decrease in the omega-3:omega-6 ratio showed a positive association with IL-6 and TNF-α production, suggesting an anti-inflammatory role of omega-3 FAs on peripheral cytokines (Kiecolt-Glaser et al., 2011). The same research group also observed anti-inflammatory properties of omega − 3 FAs rich diet in an adult population (Kiecolt-Glaser et al., 2012). Moreover, an extensive interaction between TNF-α and IL-15 has been observed at the blood brain barrier (BBB) since TNF-α enhances IL-15 synthesis and IL-15 in turn regulates TNF-α signaling at the level of the BBB (Pan et al., 2013;Pan et al., 2009). ...
Article
Background There is increasing evidence that dysregulation of polyunsaturated fatty acids (FAs) mediated membrane function plays a role in the pathophysiology of schizophrenia. Even though preclinical findings have supported the anti-inflammatory properties of omega-3 FAs on brain health, their biological roles as anti-inflammatory agents and their therapeutic role on clinical symptoms of psychosis risk are not well understood. In the current study, we investigated the relationship of erythrocyte omega-3 FAs with plasma immune markers in a clinical high risk for psychosis (CHR) sample. In addition, a mediation analysis was performed to examine whether previously reported associations between omega-3 FAs and clinical outcomes were mediated via plasma immune markers. Clinical outcomes for CHR participants in the NEURAPRO clinical trial were measured using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Scale of Assessment of Negative Symptoms (SANS) and Social and Occupational Functioning Assessment Scale (SOFAS) scales. The erythrocyte omega-3 index [eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] and plasma concentrations of inflammatory markers were quantified at baseline (n=268) and 6 month follow-up (n=146) by gas chromatography and multiplex immunoassay, respectively. In linear regression models, the baseline plasma concentrations of Interleukin (IL)-15, Intercellular adhesion molecule (ICAM)-1 and Vascular cell adhesion molecule (VCAM)-1 were negatively associated with baseline omega-3 index. In addition, 6-month change in IL-12p40 and TNF-α showed a negative association with change in omega-3 index. In longitudinal analyses, the baseline and 6 month change in omega-3 index was negatively associated with VCAM-1 and TNF-α respectively at follow-up. Mediation analyses provided little evidence for mediating effects of plasma immune markers on the relationship between omega-3 FAs and clinical outcomes (psychotic symptoms and functioning) in CHR participants. Our results indicate a predominantly anti-inflammatory relationship of omega-3 FAs on plasma inflammatory status in CHR individuals, but this did not appear to convey clinical benefits at 6 month and 12 month follow-up. Both immune and non-immune biological effects of omega-3 FAs would be resourceful in understanding the clinical benefits of omega-3 FAs in CHR papulation.
... Experimentos en modelos animales han permitido demostrar que la suplementación con ácidos grasos omega 3 producen disminución de citoquinas como la IL6 16 y afecta la hematopoiesis, reduciendo progenitores del linaje que deriva en granulocitos y monocitos 17 . En nuestro estudio el elevado contenido en ácidos grasos instaurados omega 3 y 6 del aceite de Sacha inchi, podría explicar en parte las modificaciones en las poblaciones leucocitarias hacia perfiles menos inflamatorios, en coherencia con los hallazgos de Kiecolt et al 18 . ...
Article
The postprandial stage is related to an increase in biochemical and cellular inflammatory markers. The objective of this study was to evaluate the postprandial effects of the addition of Sacha inchi oil on the concentration and size of leukocytes, erythrocytes and platelets, and on inflammation markers, after the ingestion of a high-fat meal. A sample of 42 seemingly healthy male individuals consumed two high-fat breakfast meals, one with the addition of 15mL of oil rich in polyunsaturated fatty acids (omega 3 and 6 series), extracted from Sacha Inchi seeds. Fasting blood samples were taken at 4 hours postprandial to determine hematological variables (number and size of leukocytes and platelets and percentage distribution of leukocytes) and biochemical variables such as interleukin 6 (IL6) and high-sensitivity C-Reactive protein (hs-CRP). The concentration of CRP and leukocyte and platelet counts increased following ingestion of both types of breakfast. The addition of Sacha inchi oil increased the percentage of lymphocytes (p= 0.005) and decreased that of granulocytes (p= 0.012), reversing the increase in the granulocytes / lymphocytes ratio evidenced after fat intake. The percentage of intermediate-sized cells and postprandial concentrations of IL6 also decreased. In conclusion, the addition of 15.0 mL of Sacha inchi oil to a high-fat breakfast modulates the relationship between different leukocyte populations, which could mitigate postprandial inflammatory effects and cardiovascular risk. Registration: NCT02886169.
... As they compete for the same enzymes, it is the n-6/n-3 ratio which seems to be more significant for the maintenance of a healthy metabolic milieu, with the ideal ratio reaching up to 4:1, contrary to the usual 10:1 ratio which applies for Western-type diets [30]. In a randomized controlled trial (RCT) in healthy adults, a 4-month supplementation of n-3 fatty acids of 2.5 g/d and 1.25 g/d versus placebo resulted in a significant decrease in IL-6 levels by 10% and 12% in the low and high dose n-3 FAs groups, respectively, compared to a 36% increase in the placebo group [31]. Similarly, in a 12-week study, subjects who received n-3 supplementation showed a 14% decrease in lipopolysaccharide (LPS) stimulated interleukin 6 (IL-6) production, while a decrease in the n-6:n-3 ratio led to reductions in stimulated IL-6 and TNF-α production [32]. ...
Article
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Chronic inflammation and increased oxidative stress are contributing factors to many non-communicable diseases. A growing body of evidence indicates that dietary nutrients can activate the immune system and may lead to the overproduction of pro-inflammatory cytokines. Fatty acids as macronutrients are key players for immunomodulation, with n-3 polyunsaturated fatty acids having the most beneficial effect, while polyphenols and carotenoids seem to be the most promising antioxidants. Psoriasis is a chronic, immune-mediated inflammatory disease with multifactorial etiology. Obesity is a major risk factor for psoriasis, which leads to worse clinical outcomes. Weight loss interventions and, generally, dietary regimens such as gluten-free and Mediterranean diet or supplement use may potentially improve psoriasis’ natural course and response to therapy. However, data about more sophisticated nutritional patterns, such as ketogenic, very low-carb or specific macro- and micro-nutrient substitution, are scarce. This review aims to present the effect of strictly structured dietary nutrients, that are known to affect glucose/lipid metabolism and insulin responses, on chronic inflammation and immunity, and to discuss the utility of nutritional regimens as possible therapeutic tools for psoriasis and psoriatic arthritis.
... This inconsistency may be explained by the composition of products being tested that provide different nutrients, nonuniform forms of nutrients, and an array of dosages. For example, orally administered vitamin D3 has been shown to elevate total serum 25-hydroxy vitamin D levels (denoted as serum vitamin D throughout) more robustly than the D2 form (9). Omega-3 is a nutrient that is not typically found in multivitamins but has demonstrated efficacy related to cardiovascular health (10)(11)(12). While there is disparity in the composition and efficacy of products tested, there is also the possibility of product label claims not meeting their actual analytic content when tested (13). ...
Article
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The purpose of this study was to validate the efficacy of a customized vitamin-mineral supplement on blood biomarkers in pre-menopausal females. Women (21–40 years old) who were apparently healthy were recruited from the local community (ClinicalTrials.gov trial registration NCT03828097). Pretesting (PRE) occurred in the morning 5 ± 2 days following each participant's menses and involved a fasted blood draw, body mass assessment, and blood pressure assessment. Participants were then randomly assigned in a double-blinded fashion to either the multivitamins (MV) ( n = 43) or placebo group ( n = 51). Participants consumed two capsules per day with breakfast for 12 weeks. Following the trial, participants reported to the laboratory for POST assessments, which replicated PRE procedures. Red blood cell fatty acid and serum micronutrient analyses were performed in a blinded fashion at hematology laboratories. A group × time interaction was observed for serum vitamin D levels ( p < 0.001). MV increased levels from PRE to POST (+43.7%, p < 0.001), whereas no change occurred in the placebo group. Additionally, 78% of MV participants at PRE exhibited inadequate vitamin D levels (<40 ng/dl), whereas only 30% exhibited levels below this threshold at POST. An interaction was also observed for serum folate levels ( p < 0.001). MV increased serum folate from PRE to POST ( p < 0.001), whereas no change occurred in the placebo group. Red blood cell omega-3 fatty acid content increased from PRE to POST in the MV group ( p < 0.001) and placebo group ( p < 0.05), although POST values were greater in the MV group ( p < 0.001). An interaction was observed for serum HDL cholesterol levels ( p = 0.047), and a non-significant increase in this variable from PRE to POST occurred in the MV group ( p = 0.060). Four-day food recalls indicated MV increased intake of omega-3 fatty acids, vitamin D, folate, and other micronutrients. In summary, MV supplementation increased serum vitamin D, serum folate, and red blood cell omega-3 fatty acid levels. However, these data are limited to healthy females, and more research is needed to examine if MV can affect metabolic disturbances in individuals with micronutrient deficiencies.
... Omega-3 supplementation can affect muscle directly by increasing muscle protein synthesis 156 and indirectly by decreasing systemic inflammation. 157 In 118 postmenopausal women, 6 months of fish oil-based supplementation (rich in omega-3 fatty acids) was associated with improved gait speed compared with placebo (3±16 vs -3.5±14%. 158 Furthermore, in 60 healthy older adults (aged 60-85 years), 6 months of fish oil-based omega-3 supplementation increased thigh muscle volume (mean change: 3.6% [95% CI:0.2-7.0%]), ...
Article
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The incidence and prevalence of metabolic and musculoskeletal diseases are increasing. Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, inflammation, advanced glycation end-product accumulation and increased oxidative stress. These characteristics can negatively affect various aspects of muscle health, including muscle mass, strength, quality and function through impairments in protein metabolism, vascular and mitochondrial dysfunction, and cell death. Sarcopenia is a term used to describe the age-related loss in skeletal muscle mass and function and has been implicated as both a cause and consequence of T2DM. Sarcopenia may contribute to the development and progression of T2DM through altered glucose disposal due to low muscle mass, and also increased localized inflammation, which can arise through inter- and intramuscular adipose tissue accumulation. Lifestyle modifications are important for improving and maintaining mobility and metabolic health in individuals with T2DM and sarcopenia. However, evidence for the most effective and feasible exercise and dietary interventions in this population is lacking. In this review, we discuss the current literature highlighting the bidirectional relationship between T2DM and sarcopenia, highlight current research gaps and treatments, and provide recommendations for future research.
... It reduces the production of pro-inflammatory cytokines and contributes to an increase in the number of monocytes/macrophages with the M2 (anti-inflammatory) phenotype compared to M1 (pro-inflammatory), which has a beneficial effect on inflammation and improves sensitivity to insulin (18) . All this leads to a decrease in serum levels of inflammatory markers, such as high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor α (TNF-α), IL-6 or IL-1β (19,20). Longterm use of PUFAs may also reduce chemotaxis of both monocytes and neutrophils (21) . ...
Article
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Cardiovascular diseases are the leading cause of mortality worldwide. Prevention, diagnosis and treatment of these diseases are one of the major challenges in modern medicine. Despite a large number of pharmacological agents significantly reducing the cardiovascular risk, it is still high in many patients. Due to the multifactorial aetiology and complex pathomechanism of cardiovascular diseases, the development of a more effective therapy remains an open issue. It was found in the 1980s that a diet rich in polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid in particular, was associated with a lower incidence of cardiovascular diseases. For this reason, polyunsaturated fatty acids have become the subject of many clinical trials aimed at understanding their mechanism of action and determining their exact impact on cardiovascular risk. Polyunsaturated fatty acids are known to affect many aspects that are key factors in the development of cardiovascular disease. They are characterised mainly by a positive effect on the structure and functioning of cell membranes, the ability to reduce inflammation and blood pressure, anticoagulant and antiplatelet effects, antiarrhythmic activity, the ability to improve myocardial contractility and a beneficial effect on the lipid profile. The latest analyses of the available clinical trials show that these compounds reduce cardiovascular risk in both primary and secondary prevention. Therefore, they represent a promising therapeutic option. It is worth noting that the effect seems to depend on the type of polyunsaturated fatty acids, their dose and individual factors. Nevertheless, this issue is extremely complex and requires further research to fully understand the mechanism of action and establish ideal therapeutic doses to improve patient prognosis.
... TNF-α: MeDi + olive oil, 95 % CI -2.7, -1.1, p = 0.006; IFN-γ: MeDi+nuts, 95 % CI -10.0, -0.6, p = 0.03) at 5 years follow up [220,221]. Likewise, reduced circulating inflammatory biomarkers and oxidative stress have been reported in middle-aged and older adults who maintained fish oil and omega-3 s supplementation [222,223]. Indeed, it has been suggested that systemic inflammation is itself a moderator between the effects of diet and cognition [224]. In light of these findings, as well as the direct association between systemic inflammation and neuroinflammation, it is possible that healthy dietary supplements may have the potential to exert cognitive benefits by attenuating systemic inflammation, which can subsequently suppress aberrant microglia-mediated neuroinflammation in aging. ...
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Given the increasing prevalence of age-related cognitive decline, it is relevant to consider the factors and mechanisms that might facilitate an individual’s resiliency to such deficits. Growing evidence suggests a preeminent role of microglia, the prime mediator of innate immunity within the central nervous system. Human and animal investigations suggest aberrant microglial functioning and neuroinflammation are not only characteristic of the aged brain, but also might contribute to age-related dementia and Alzheimer’s Disease. Conversely, accumulating data suggest that modifiable lifestyle factors (MLFs), such as healthy diet, exercise and cognitive engagement, can reliably afford cognitive benefits by potentially suppressing inflammation in the aging brain. The present review highlights recent advances in our understanding of the role for microglia in maintaining brain homeostasis and cognitive functioning in aging. Moreover, we propose an integrated, mechanistic model that postulates an individual’s resiliency to cognitive decline afforded by MLFs might be mediated by the mitigation of aberrant microglia activation in aging, and subsequent suppression of neuroinflammation.
... Normal physiological modifications to the brain with aging comprise reduction of n-3 LC-PUFA and brains of AD patients have lower DHA levels. It has been reported that DHA supplementation can reduce inflammatory markers and oxidative stress after DHA supplementation in healthy middle-aged and older adults [72]. Furthermore, DHA supplementation showed a decreased IL6 expression in the hippocampus of adult C57Bl/6 Mice [73]. ...
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Keywords: Fatty acid desaturase 1 (FADS1) Fatty acid desaturase 2 (FADS2) Elongation of very-long-chain fatty acids-like 2 (ELOVL2) Single nucleotide polymorphism (SNP) Alzheimer's disease (AD) polyunsaturated fatty acids (PUFAs) Arachidonic acid (AA) A B S T R A C T Polyunsaturated fatty acids (PUFAs) are closely related to various physiological conditions. In several age-related diseases including Alzheimer's disease (AD) altered PUFAs metabolism has been reported. However, the mechanism behind PUFAs impairment and AD developpement remains unclear. In humans, PUFAs biosynthesis requires delta-5 desaturase (D5D), delta-6 desaturase (D6D) and elongase 2 activities; which are encoded by fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongation of very-long-chain fatty acids-like 2 (ELOVL2) genes, respectively. In the present work, we aim to assess whether genetic variants in FADS1, FADS2 and ELOVL2 genes influence plasma and erythrocyte PUFA composition and AD risk. A case-control study was carried out in 113 AD patients and 161 healthy controls.Rs174556, rs174617, and rs3756963 of FADS1, FADS2, and ELOVL2 genes, respectively were genotyped using PCR-RFLP. PUFA levels were quantified using Gas Chromatography. Genotype distributions of rs174556 (FADS1) and rs3756963 (ELOVL2) were different between case and control groups. The genotype TT of rs174556 and rs3756963 single nucleotide polymorphism (SNP) increases significantly the risk of AD in our population. PUFA analysis showed higher plasma and erythrocyte arachidonic acid (AA) level in patients with AD, whereas only plasma docosahexaenoic acid (DHA) was significantly decreased in AD patients. The indexes AA/Dihomo-gamma-linolenic acid (DGLA) and C24:4n-6/ Adrenic acid (AdA) were both higher in the AD group. Interestingly, patients with TT genotype of rs174556 presented higher AA level and AA/DGLA index in both plasma and erythrocyte. In addition, higher AA and AA/ DGLA index were observed in erythrocyte of TT genotype ofrs3756963 carrier's patients. Along with, positive correlation between AA/DGLA index, age or Gamma-linolenic acid (GLA)/ Linoleic acid (LA) index was seen in erythrocyte and /or plasma of AD patients. After adjustment for confounding factors, the genotype TT of rs174556, erythrocyte AA and AA/DGLA index were found to be predictive risk factors for AD while plasma DHA was found associated with lower AD risk. Both rs174556 and rs3756963 influence AD risk in the Tunisian population and they are likely associated with high AA level. The combination of the two variants increases further the susceptibility to AD. We suggest that FADS1 and ELOVL2 variants could likely regulate the efficiency of AA biosynthesis which could be at the origin of inflammatory derivate.
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Certain omega‐3 fatty acids, such as α‐linolenic acid (ALA), and omega‐6 fatty acids, such as linoleic acid (LA), cannot be synthesized in the human body and are recognized as essential fatty acids. While some long‐chain polyunsaturated fatty acids (LC‐PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be synthesized from the parent omega‐3 fatty acids (ALA), this is done at a very low conversion rate, hence it must be taken through diet to fulfill the daily intake requirement. Both EPA and DHA have several vital activities in the human body, such as anti‐inflammatory effects and being the structural component of the cell membrane. The fatty acids DHA, arachidonic acid (AA), and LA accumulate most usually in tissues, whereas DHA mostly accumulates in retina and brain gray matters and it is important for proper visual and neurological development during gestation period and postnatal period. Replacement of saturated fatty acids with omega‐3 and omega‐6 fatty acids in daily diet reduces the risk of cardiovascular disease and prevents diseases such as Alzheimer's, bipolar disorder, and schizophrenia. Proper EPA and DHA content also help individuals with type 2 diabetes to reduce the elevated serum triacylglycerides. It also facilitates infants to reduce the risks of fatal myocardial infarction and other cardiovascular diseases. Hence, as recommended by the American Heart Association, it is necessary to consume fish, and especially oily fish at least twice per week as it is an excellent source of these fatty acids. Marine fishes of Salmonidae, Scombridae, and Clupeidae families are important sources of omega‐3 fatty acids but due to the increasing demand of PUFA and diminishing aquatic ecosystem, fishes are not a sustainable source to serve as a long‐term feed‐stock for omega‐3. Plants can synthesize some of PUFA such as oleic acid, LA, GLA (γ‐linolenic acid), ALA, and octadecatetraenoic acid but due to lacking some essential enzymes for PUFA synthesis such as desaturase and elongases, they are incapable of synthesizing EPA and DHA. Oleaginous microalgae and thraustochytrids could be a sustainable option to produce microbial EPA and DHA.
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The consumption of omega-3 (n-3) and omega-6 (n-6) essential fatty acids in Western diets is thought to have changed markedly during the 20th century. We sought to quantify changes in the apparent consumption of essential fatty acids in the United States from 1909 to 1999. We calculated the estimated per capita consumption of food commodities and availability of essential fatty acids from 373 food commodities by using economic disappearance data for each year from 1909 to 1999. Nutrient compositions for 1909 were modeled by using current foods (1909-C) and foods produced by traditional early 20th century practices (1909-T). The estimated per capita consumption of soybean oil increased >1000-fold from 1909 to 1999. The availability of linoleic acid (LA) increased from 2.79% to 7.21% of energy (P < 0.000001), whereas the availability of α-linolenic acid (ALA) increased from 0.39% to 0.72% of energy by using 1909-C modeling. By using 1909-T modeling, LA was 2.23% of energy, and ALA was 0.35% of energy. The ratio of LA to ALA increased from 6.4 in 1909 to 10.0 in 1999. The 1909-T but not the 1909-C data showed substantial declines in dietary availability (percentage of energy) of n-6 arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Predicted net effects of these dietary changes included declines in tissue n--3 highly unsaturated fatty acid status (36.81%, 1909-T; 31.28%, 1909-C; 22.95%, 1999) and declines in the estimated omega-3 index (8.28, 1909-T; 6.51, 1909-C; 3.84, 1999). The apparent increased consumption of LA, which was primarily from soybean oil, has likely decreased tissue concentrations of EPA and DHA during the 20th century.
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Preclinical evidence of the preventive benefits of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in breast cancer continues to fuel interest in the potential role of dietary fat content in reducing breast cancer risk. The dose of fish-oil/omega-3 PUFAs needed to achieve maximal target tissue effects for breast cancer prevention remains undefined. To determine the dose effects of omega-3 fatty acids on breast adipose tissue fatty acid profiles, we conducted a study of 4 doses of omega-3 PUFAs in women at high risk of breast cancer. In this 6-mo randomized open-label study, 48 women with increased breast cancer risk received 1, 3, 6, or 9 capsules/d of an omega-3 PUFA supplement that provided 0.84, 2.52, 5.04, and 7.56 g docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) daily, respectively. Subjects made monthly visits, at which time pill counts were made and fasting blood samples were collected to determine fatty acid profiles; anthropometric measurements were made, breast adipose tissue samples were collected, and laboratory tests of toxicity (alanine aminotransferase, LDL cholesterol, and platelet function) were made at baseline and at 3 and 6 mo. All doses led to increased serum and breast adipose tissue EPA and DHA concentrations, but the response to 0.84 g DHA+EPA/d was less than the maximum possible response with > or = 2.52 g/d. Body mass index attenuated the dose response for serum tissue DHA and EPA (P = 0.015 and 0.027, respectively) and breast adipose tissue DHA (P = 0.0022) in all of the treatment groups. The incremental increase in DHA and EPA correlated inversely with baseline fat and serum values. Compliance over 6 mo was 92.9 +/- 9.2% and was unaffected by treatment arm. No severe or serious toxicities were reported. Daily doses up to 7.56 g DHA+EPA were well tolerated with excellent compliance in this cohort at high risk of breast cancer. Body mass index and baseline fatty acid concentrations modulated the dose-response effects of omega-3 PUFA supplements on serum EPA and DHA and breast adipose tissue DHA.
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The debate over a role for n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) in depressed mood continues. The objective was to update a previous systematic review and meta-analysis of published randomized controlled trials investigating the effects of n-3 PUFAs on depressed mood and to explore potential sources of heterogeneity. Eight databases were searched for trials that randomly assigned participants to receive n-3 PUFAs/fish, measured depressed mood, used human participants, and included a comparison group up to April 2009. Thirty-five randomized controlled trials were identified; 17 were not included in the previous review. The pooled standardized difference in mean outcome of the 29 trials that provided data to allow pooling (fixed-effects model) was 0.10 SD (95% CI: 0.02, 0.17) in those who received n-3 PUFAs compared with placebo, with strong evidence of heterogeneity (I(2) = 65%, P < 0.01). The presence of funnel plot asymmetry suggested that publication bias was a likely source of this heterogeneity. Depressive symptom severity and participant diagnosis also explained some of the observed heterogeneity. Greater effects of n-3 PUFAs were found in individuals with more-severe depressive symptoms. In trials that enrolled individuals with a diagnosed depressive disorder, the combined mean difference was 0.41 (95% CI: 0.26, 0.55), although evidence of heterogeneity was also found (I(2) = 71%). In trials that enrolled individuals without a depressive diagnosis, no beneficial effects of n-3 PUFAs were found (largest combined mean difference: 0.22; 95% CI: -0.01, 0.44; I(2) = 0%). Trial evidence of the effects of n-3 PUFAs on depressed mood has increased but remains difficult to summarize because of considerable heterogeneity. The evidence available provides some support of a benefit of n-3 PUFAs in individuals with diagnosed depressive illness but no evidence of any benefit in individuals without a diagnosis of depressive illness.
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Polyunsaturated fatty acids can have beneficial effects on human immune cells, such as peripheral blood mononuclear cells (PBMCs). However, the mechanisms of action of polyunsaturated fatty acids on immune cells are still largely unknown. The objective was to examine the effects of supplementation with the polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on whole-genome PBMC gene expression profiles, in healthy Dutch elderly subjects participating in a double-blind trial, by using whole-genome transcriptomics analysis. The subjects were randomly allocated to 1 of 3 groups: 1) consumption of 1.8 g EPA+DHA/d (n = 36), 2) consumption of 0.4 g EPA+DHA/d (n = 37), or 3) consumption of 4.0 g high-oleic acid sunflower oil (HOSF)/d (n = 38). All supplements were given in capsules. Before and after 26 wk of intervention, blood samples were collected. Microarray analysis was performed on PBMC RNA from 23 subjects who received 1.8 g EPA+DHA/d and 25 subjects who received HOSF capsules. Quantitative real-time polymerase chain reaction was performed in all 111 subjects. A high EPA+DHA intake changed the expression of 1040 genes, whereas HOSF intake changed the expression of only 298 genes. EPA+DHA intake resulted in a decreased expression of genes involved in inflammatory- and atherogenic-related pathways, such as nuclear transcription factor kappaB signaling, eicosanoid synthesis, scavenger receptor activity, adipogenesis, and hypoxia signaling. These results are the first to show that intake of EPA+DHA for 26 wk can alter the gene expression profiles of PBMCs to a more antiinflammatory and antiatherogenic status. This trial was registered at clinicaltrials.gov as NCT00124852.
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Despite well-known benefits of physical activity for older adults, about two thirds are underactive. Community-based programs are needed to facilitate increased physical activity. We examine the effectiveness of CHAMPS II, an inclusive, choice-based physical activity promotion program to increase lifetime physical activity levels of seniors. CHAMPS guided participants to choose activities that took into account their health, preferences, and abilities. It offered information on ways for them to exercise safely, motivate themselves, overcome barriers, and develop a balanced exercise regimen. A 1-year randomized controlled trial was conducted with physically underactive seniors in a multispecialty group practice. Changes in self-reported physical activity by group were evaluated using ANCOVA, controlling for age and sex. Of 173 randomized subjects, 164 (95%) completed the trial. Subjects were aged 65 to 90 years (M = 74, SD = 6); 66% were female. The intervention group increased estimated caloric expenditure by 487 calories/week in moderate (or greater) intensity activities (MET >/= 3.0; p <.001) and by 687 calories/week in physical activities of any intensity (p <.001). Control group changes were negligible. Between-group analyses found that the changes were significantly different in both measures (p values <.05). Overweight persons especially benefited from this program. The program was as effective for women, older adults (75+), and those who did not set aside time to exercise at baseline. The program led to meaningful physical activity increases. Individually tailored programs to encourage lifestyle changes in seniors may be effective and applicable to health care and community settings.
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Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oil-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--are more biologically potent than alpha-linolenic acid (ALA). Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn's disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB(4) produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.
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overview measures of depression provides brief descriptions of each measure and summarizes the available psychometric data / the measures fall into the following categories: structured diagnostic interviews, clinician rating scales, global illness ratings, and self-report instruments what to measure / requirements of measures / target populations / survey of measures / related domains / when to measure (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are precursors of potent lipid mediators, termed eicosanoids, which play an important role in the regulation of inflammation. Eicosanoids derived from n-6 PUFAs (e.g., arachidonic acid) have proinflammatory and immunoactive functions, whereas eicosanoids derived from n-3 PUFAs [e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] have anti-inflammatory properties, traditionally attributed to their ability to inhibit the formation of n-6 PUFA-derived eicosanoids. While the typical Western diet has a much greater ratio of n-6 PUFAs compared with n-3 PUFAs, research has shown that by increasing the ratio of n-3 to n-6 fatty acids in the diet, and consequently favoring the production of EPA in the body, or by increasing the dietary intake of EPA and DHA through consumption of fatty fish or fish-oil supplements, reductions may be achieved in the incidence of many chronic diseases that involve inflammatory processes; most notably, these include cardiovascular diseases, inflammatory bowel disease (IBD), cancer, and rheumatoid arthritis, but psychiatric and neurodegenerative illnesses are other examples.
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On the basis of evidence from studies showing the antidepressant effects of omega-3 polyunsaturated fatty acids and the inverse relation between fish consumption and the prevalence of depression, the phospholipid hypothesis seems promising in ascertaining the etiology and treatment of depression. Although several studies have shown lower levels of omega-3 (n-3) polyunsaturated fatty acids in depressive patients, the results of individual polyunsaturated fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and the omega-6 (n-6) polyunsaturated fatty acid arachidonic acid (AA), were inconsistent. We conducted the meta-analyses of 14 studies comparing the levels of polyunsaturated fatty acids between depressive patients and control subjects. The effect size of each study was synthesized by using a random effects model. Compared with control subjects, the levels of EPA, DHA, and total n-3 polyunsaturated fatty acids were significantly lower in depressive patients. There was no significant change in AA or total n-6 polyunsaturated fatty acids. The results showed lower levels of EPA, DHA, and total n-3 polyunsaturated fatty acids in patients with depression, thus implying that n-3 polyunsaturated fatty acids play a role in the pathogenesis of depression. Our findings provide further support to the phospholipid hypothesis of depression and a rationale for using n-3 polyunsaturated fatty acids as an alternative treatment for depression. With these results, future studies examining specific roles of DHA and EPA in different clusters of depressive symptoms are warranted.
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Obesity and related metabolic conditions are of epidemic proportions in most of the world, affecting both adults and children. The accumulation of lipids in the body in the form of white adipose tissue in the abdomen is now known to activate innate immune mechanisms. Lipid accumulation causes adipocytes to directly secrete the cytokines interleukin (IL) 6 and tumor necrosis factor alpha (TNFalpha), but also monocyte chemoattractant protein 1 (MCP-1), which results in the accumulation of leukocytes in fat tissue. This sets up a chronic inflammatory state which is known to mediate the association between obesity and conditions such as cardiovascular disease, type 2 diabetes, and cancer. There is also a substantial literature linking inflammation with risk for depression. This includes the observations that: (1) people with inflammatory diseases such as multiple sclerosis, cardiovascular disease, and psoriasis have elevated rates of depression; (2) many people administered inflammatory cytokines such as interferon alpha develop depression that is indistinguishable from depression in non-medically ill populations; (3) a significant proportion of depressed persons show upregulation of inflammatory factors such as IL-6, C-reactive protein, and TNFalpha; (4) inflammatory cytokines can interact with virtually every pathophysiologic domain relevant to depression, including neurotransmitter metabolism, neuroendocrine function, and synaptic plasticity. While many factors may contribute to the association between inflammatory mediators and depression, we hypothesize that increased adiposity may be one causal pathway. Mediational analysis suggests a bi-directional association between adiposity and depression, with inflammation possibly playing an intermediary role.
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Blood lipids and inflammatory markers levels have been associated with the development and progression of atherosclerosis. As the association of inflammatory markers with plasma fatty acids has not been extensively evaluated and understood, we sought to investigate the associations between dietary and plasma fatty acids with various inflammation and coagulation markers. High sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), fibrinogen, and homocysteine were measured in serum of 374 free-living, healthy men and women, randomly selected from the ATTICA's study database. Total plasma fatty acids were determined by gas chromatography. Dietary fatty acids were assessed through a semi-quantitative FFQ. Multi-adjusted regression analyses revealed that plasma n-3 fatty acids were inversely associated with CRP, IL-6 and TNF-alpha; plasma n-6 fatty acids were inversely associated with CRP, IL-6 and fibrinogen; monounsaturated fatty acids were inversely associated with CRP and IL-6 (all p-values<0.05). Interestingly, the n-6/n-3 ratios exhibited the strongest positive correlations with all the markers studied. No associations were observed between dietary fatty acids and the investigated markers. Measurements of total plasma fatty acids could provide insights into the relationships between diet and atherosclerotic disease. Moreover, the n-6/n-3 ratio may constitute a predictor of low-grade inflammation and coagulation.
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The evidence for the cardioprotective nature of omega-3 fatty acids is abundant, and currently available data indicate that patients with known coronary heart disease should consume at least 1 g daily of long-chain omega-3 fatty acids from either oily fish or fish-oil supplements, and that individuals without disease should consume at least 250-500 mg daily. However, this area of research poses two questions. Firstly, which is the best source of omega-3 fatty acids-fish or fish-oil supplements? Secondly, are recommendations for omega-3 supplementation warranted in view of the rapid depletion of world fish stocks? The argument that eating fish is better than taking fish-oil supplements stems from the fact that several important nutrients, such as vitamin D, selenium, and antioxidants, are missing from the supplements. However, three major prevention trials have clearly indicated that omega-3 fatty acid capsules confer cardiovascular benefits and, therefore, that both are cardioprotective. Sustainable sources of omega-3 fatty acids will need to be identified if long-term cardiovascular risk reduction is to be achieved at the population level.
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Dietary intake of polyunsaturated n-3 fatty acids has been associated with a reduced incidence of adverse cardiovascular events. The protective mechanisms involved are not fully understood, but may include anti-inflammatory factors. We sought to investigate the relationship between n-3 fatty acid levels in erythrocyte membranes and markers of systemic inflammation in 992 individuals with stable coronary artery disease. Cross-sectional associations of C-reactive protein (CRP) and Interleukin-6 (Il-6) with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EHA) were evaluated in multivariable linear regression models adjusted for demographics, cardiovascular risk factors, medication use, exercise capacity, body-mass index, and waist-to-hip ratio. After multivariable adjustment, n-3 fatty acid levels (DHA+EPA) were inversely associated with CRP and IL-6. The inverse association of n-3 fatty acids with CRP and IL-6 was not modified by demographics, body-mass index, smoking, LDL-cholesterol, or statin use (p values for interaction>0.1). In patients with stable coronary artery disease, an independent and inverse association exists between n-3 fatty acid levels and inflammatory biomarkers. These findings suggest that inhibition of systemic inflammation may be a mechanism by which n-3 fatty acids prevent recurrent cardiovascular events.
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Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as "myokines." Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.