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Omega-3 Supplementation Lowers Inflammation and Anxiety in Medical Students: A Randomized Controlled Trial
Abstract
Observational studies have linked lower omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and higher omega-6 (n-6) PUFAs with inflammation and depression, but randomized controlled trial (RCT) data have been mixed. To determine whether n-3 decreases proinflammatory cytokine production and depressive and anxiety symptoms in healthy young adults, this parallel group, placebo-controlled, double-blind 12-week RCT compared n-3 supplementation with placebo. The participants, 68 medical students, provided serial blood samples during lower-stress periods as well as on days before an exam. The students received either n-3 (2.5 g/d, 2085 mg eicosapentaenoic acid and 348 mg docosahexanoic acid) or placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Compared to controls, those students who received n-3 showed a 14% decrease in lipopolysaccharide (LPS) stimulated interleukin 6 (IL-6) production and a 20% reduction in anxiety symptoms, without significant change in depressive symptoms. Individuals differ in absorption and metabolism of n-3 PUFA supplements, as well as in adherence; accordingly, planned secondary analyses that used the plasma n-6:n-3 ratio in place of treatment group showed that decreasing n-6:n-3 ratios led to lower anxiety and reductions in stimulated IL-6 and tumor necrosis factor alpha (TNF-α) production, as well as marginal differences in serum TNF-α. These data suggest that n-3 supplementation can reduce inflammation and anxiety even among healthy young adults. The reduction in anxiety symptoms associated with n-3 supplementation provides the first evidence that n-3 may have potential anxiolytic benefits for individuals without an anxiety disorder diagnosis. ClinicalTrials.gov identifier: NCT00519779.
... The results support the use of omega-3 fatty acids as a complementary approach alongside traditional pharmacologic treatments for low back pain, potentially improving patient outcomes with fewer side effects. 10,14 Magnesium supplementation has shown robust effects in reducing anxiety in craniofacial inflammation models. Magnesium's anxiolytic properties are believed to stem from its ability to regulate HPA axis activity and modulate neuroinflammation. ...
... Its effects are thought to be linked to its antiinflammatory properties, particularly through the inhibition of inflammatory cytokines like TNFα and IL-6, and its ability to increase BDNF levels, which are critical for mood regulation and neurogenesis. 12,14 Probiotics, though studied in fewer trials, also showed promise in reducing anxiety-like behaviors in craniofacial inflammation models. Probiotics modulate the gut-brain axis, which is increasingly recognized as an important pathway for regulating neuroinflammation and neurotransmitter systems like serotonin. ...
... Omega-3 fatty acids and magnesium were the most extensively investigated, with multiple studies reporting positive outcomes. 10,11,14 Curcumin also showed strong efficacy, while probiotics had more limited but promising evidence. 12,13 Despite their differences, these nutritional strategies all seem to share a common mechanism of reducing neuroinflammation, either through direct modulation of immune responses or by enhancing brain neuroplasticity. ...
Introduction: Craniofacial inflammatory conditions, such as temporomandibular joint disorders and periodontitis, are often linked to heightened anxiety-like responses. Emerging evidence suggests that nutritional strategies may serve as effective, non-pharmacological approaches to mitigate anxiety under such conditions. Objective: To systematically review the evidence on the anxiolytic effects of dietary strategies, such as omega-3 fatty acids, magnesium, probiotics, and curcumin, in individuals or animal models experiencing craniofacial inflammatory conditions. Methods: PubMed, Scopus, and Web of Science were systematically searched for studies published up to January 2025. Studies were included if they evaluated the impact of nutritional interventions on anxiety outcomes in populations with craniofacial inflammation. Relevant data on the study population, interventions, and outcomes were extracted and summarized. Review/Discussion: Five studies were included, comprising human and animal research. Omega-3 fatty acids and magnesium supplementation were associated with reduced anxiety scores and inflammatory markers. Probiotics showed improvement in psychological symptoms and systemic inflammation. Curcumin demonstrated anxiolytic effects by reducing oxidative stress, with combined omega-3 and curcumin showing synergistic benefits. Despite promising results, significant variability in methodologies and outcome measures limits the generalizability of findings. Conclusion: Nutritional strategies hold promise for reducing anxiety in craniofacial inflammatory conditions. Further research with standardized protocols is needed to validate these findings and inform clinical applications.
... Existing evidence on the efficacy of supplementation with omega-3 fatty acids in reducing anxiety symptoms is insufficient. An intervention trial revealed that omega-3 could improve anxiety among healthy subjects who encountered stressful evaluations [21]. A review study that evaluated the effects of omega-3 on anxiety indicated an improvement in anxiety symptoms (2.1 g/d EPA); however, the number of studies was very low (n = 1) [22]. ...
... After excluding 146 duplicates and an additional 2029 records through screening the title and abstract, 40 full texts were assessed for eligibility. Overall, 23 trials with 2,189 participants were eligible for inclusion in this dose-response meta-analysis [21,. The between-reviewer agreement for including studies was near perfect (Cohen's kappa = 0.85) at the full-text screening step. ...
... Of the 23 trials, eight were conducted in participants with normal weight [42,43,45,51,52,55,59,60], seven trials were conducted in those with overweight [44,45,48,53,55,57,62], and three in those with obesity [46,47,54]. Seven trials did not report the weight status of the participants in the study [21,49,50,56,58,61,63]. Nineteen out of the 23 trials had an intervention period of 12 weeks or less [21, 42-55, 57, 58, 60, 61], and the other four trials had an intervention duration longer than 12 weeks [56,59,62,63]. ...
Background/Objectives
There is uncertainty about the optimum dose of omega-3 fatty acids for anxiety symptoms. We aimed to find the dose-dependent effect of omega-3 supplementation on anxiety symptoms.
Methods
We systematically reviewed PubMed, Scopus, and Web of Science until December 2022 to find randomized trials that assessed the effects of omega-3 fatty acids supplementation on anxiety symptoms in adults. Investigators performed the literature search and screened the titles/abstracts and full-texts and between-reviewer agreement was assessed as Cohen’s kappa coefficient. We conducted a random-effects dose-response meta-analysis to estimate standardized mean differences (SMD) and 95% confidence intervals (CIs) and assessed the certainty of evidence using the GRADE framework.
Results
A total of 23 trials with 2189 participants were included. Each 1 gram per day supplementation with omega-3 fatty acids resulted in a moderate decrease in anxiety symptoms (SMD: -0.70, 95%CI: -1.17, -0.22; GRADE = low). The non-linear dose-response analysis indicated the greatest improvement at 2 g/d (SMD: -0.93, 95%CI: -1.85, -0.01), and that supplementation in a dose lower than 2 g/d did not affect anxiety symptoms. Omega-3 fatty acids did not increase adverse events (odds ratio: 1.20, 95%CI: 0.89, 1.61; GRADE = moderate).
Conclusions
The present dose-response meta-analysis suggested evidence of very low certainty that supplementation with omega-3 fatty acids may significantly improve anxiety symptoms, with the greatest improvements at 2 g/d. More trials with better methodological quality are needed to reach more robust evidence.
Protocol registration
PROSPERO (CRD42022309636).
... deficient versus supplemented. 8 BOGACHUK, JACOBS, AND MOGHADDAM PUFA deficiency to inflammatory processes and microglia structure and function (Decoeur et al., 2022;Kiecolt-Glaser et al., 2011), we also assessed the impact of this dietary model and supplementation on microglial morphology in multiple brain regions. We find that n-3 PUFA deficiency and supplementation influence anxiety in a contextand sex-specific manner and produce brain region-specific effects on microglia. ...
... The DIETARY OMEGA-3 FATTY ACIDS AND ADOLESCENT ANXIETY relationship of n-3 PUFAs to anxiety and anxiety disorders has been difficult to determine (Natacci et al., 2018;Sanchez-Villegas et al., 2007). In particular, supplementation of n-3 PUFAs has yielded conflicting results that depend on the underlying clinical diagnosis, demographic differences among participants, and the precise measurements being used (Buydens-Branchey et al., 2008;Fux et al., 2004;Kiecolt-Glaser et al., 2011;Haberka et al., 2013; also see Reily et al., 2023). Consequently, recent meta-analyses suggest that while n-3 PUFA intake is associated with improved anxiety phenotype, these effects are difficult to interpret due to differences in overall design of the studies (Deane et al., 2021;Su et al., 2018). ...
... Region-Specific Effects on Microglia n-3 PUFAs and their metabolites exhibit anti-inflammatory effects in the brain (Hjorth & Freund-Levi, 2012;Johnson, 2015;Orr et al., 2013). Some of the recent studies that have reported positive outcomes of anxiety treatment in adolescents and young adults with n-3 PUFA supplementation have found corresponding changes in inflammatory markers (Jamilian et al., 2018;Kiecolt-Glaser et al., 2011). This correlation has been seen in other conditions, such as traumatic brain injury models, where treatment with n-3 PUFAs helped regulate microglial polarization to less inflammatory states (X. ...
Dietary maternal deficiency in omega-3 polyunsaturated fatty acids (n-3 PUFA) is a potential risk factor for the development of anxiety and other mood disorders in children and adolescents. Here, we used a previously characterized maternal n-3 PUFA dietary deficiency model in rats to determine the impact of postweaning supplementation on adolescent anxiety-like behaviors. We focused on two models of anxiety: innate anxiety tested by the elevated plus maze and a novel operant model of learned anxiety where animals learn that actions may be associated with a variable probability of harm. Given that recent basic and clinical studies have associated anxiety and other adverse effects of n-3 PUFA deficiency on inflammatory processes and microglial structure and function, we also assessed the impact of our dietary deficiency model and supplementation on adolescent microglial morphology in multiple brain regions. We found that the male and female adolescent n-3 PUFA-deficient groups exhibit increased innate anxiety, but only females showed enhanced learned anxiety. Supplementation after weaning did not significantly affect innate anxiety but ameliorated learned anxiety in females. Thus, the beneficial effects of supplementation on adolescent anxiety may be sex-specific and depend on the type of anxiety. We also found that n-3 PUFA deficiency influences microglia function in adolescents in the amygdala and nigrostriatal, but not mesolimbic, brain regions. Collectively, these data suggest that while n-3 PUFA dietary supplementation may be effective in reducing adolescent anxiety, this effect is context-, sex-, and brain network-specific.
... Fifty-three trials reported information on depression severity, of those, seven trials reported information on depression remission (online Supplementary Table 7). Of the fiftythree studies, ten trials were carried out on healthy participants (53,55,58,62,64,67,94,(101)(102)(103) , twenty-five trials were carried out in depressed populations (39,41,(43)(44)(45)49,51,56,65,66,70,73,76,(79)(80)(81)87,88,90,92,93,96,98,99,105) , one study in Alzheimer's disease patients (38) , two in participants with borderline personality disorder (40,104) , one in those with stress (42) , one in patients with myocardial infarction (57,60) , one in patients with selfharm experience (61) , one in those with mild cognitive impairment (69) , one in those with psychological distress (71) , one in people at risk for psychotic disorders (77) , two in those with bipolar disorders (78,79) , one in those with schizophrenia (82) , two in patients with Parkinson's disease (83,89) , one in patients with ischemic stroke (84) , one in women with premenstrual syndrome (95) and one those with cognitive decline (103) . Twelve trials had a low risk of bias (39,41,42,58,66,70,71,74,77,83,89,101) , sixteen trials were rated to have some concerns (46,53,55,65,76,78,79,81,82,84,90,(92)(93)(94)98,102,103) and the other twenty-five trials considered to have a high risk of bias (38,40,(43)(44)(45)48,49,51,56,57,(60)(61)(62)64,67,69,73,80,87,88,95,96,99,104) . ...
... Of the fiftythree studies, ten trials were carried out on healthy participants (53,55,58,62,64,67,94,(101)(102)(103) , twenty-five trials were carried out in depressed populations (39,41,(43)(44)(45)49,51,56,65,66,70,73,76,(79)(80)(81)87,88,90,92,93,96,98,99,105) , one study in Alzheimer's disease patients (38) , two in participants with borderline personality disorder (40,104) , one in those with stress (42) , one in patients with myocardial infarction (57,60) , one in patients with selfharm experience (61) , one in those with mild cognitive impairment (69) , one in those with psychological distress (71) , one in people at risk for psychotic disorders (77) , two in those with bipolar disorders (78,79) , one in those with schizophrenia (82) , two in patients with Parkinson's disease (83,89) , one in patients with ischemic stroke (84) , one in women with premenstrual syndrome (95) and one those with cognitive decline (103) . Twelve trials had a low risk of bias (39,41,42,58,66,70,71,74,77,83,89,101) , sixteen trials were rated to have some concerns (46,53,55,65,76,78,79,81,82,84,90,(92)(93)(94)98,102,103) and the other twenty-five trials considered to have a high risk of bias (38,40,(43)(44)(45)48,49,51,56,57,(60)(61)(62)64,67,69,73,80,87,88,95,96,99,104) . In total, twenty trials were carried out in populations with overweight or obesity (BMI ≥ 25 kg/m 2 ) (38,(41)(42)(43)45,48,57,58,(65)(66)(67)69,71,84,94,98,99,101) , eight trials were conducted in participants with normal weight (18 < BMI < 25 kg/m 2 ) (39,61,62,64,81,89,90,95) and the other twenty-seven trials did not report the weight status of the participants (40,49,51,53,55,56,60,67,70,73,74,(76)(77)(78)(79)(80)82,83,87,88,92,93,96,(102)(103)(104)(105) . ...
... Twelve trials had a low risk of bias (39,41,42,58,66,70,71,74,77,83,89,101) , sixteen trials were rated to have some concerns (46,53,55,65,76,78,79,81,82,84,90,(92)(93)(94)98,102,103) and the other twenty-five trials considered to have a high risk of bias (38,40,(43)(44)(45)48,49,51,56,57,(60)(61)(62)64,67,69,73,80,87,88,95,96,99,104) . In total, twenty trials were carried out in populations with overweight or obesity (BMI ≥ 25 kg/m 2 ) (38,(41)(42)(43)45,48,57,58,(65)(66)(67)69,71,84,94,98,99,101) , eight trials were conducted in participants with normal weight (18 < BMI < 25 kg/m 2 ) (39,61,62,64,81,89,90,95) and the other twenty-seven trials did not report the weight status of the participants (40,49,51,53,55,56,60,67,70,73,74,(76)(77)(78)(79)(80)82,83,87,88,92,93,96,(102)(103)(104)(105) . The intervention duration was 12 weeks or shorter in thirtyone trials (39)(40)(41)(42)(43)(44)48,49,60,61,(64)(65)(66)(67)70,71,73,74,76,80,81,84,87,88,90,93,95,96,99,104,105) , between 12 and 24 weeks in nine trials (51,56,58,83,89,92,94,98,103) , and longer than 24 weeks in thirteen trials (38,43,53,55,57,62,69,(77)(78)(79)82,101,102) . ...
We aimed to investigate the effectiveness of omega-3 fatty acids supplementation on the risk of developing depression, depressive symptoms and remission of depression. We searched PubMed, Scopus, and Web of Science from inception to December 2022 to find randomized trials of omega-3 fatty acids supplementation in adults. We conducted random-effects meta-analyses to estimate standardized mean differences (SMD) and 95% confidence intervals (CIs) for continuous outcomes and risk difference and 95%CI for binary outcomes. A total of 67 trials were included. Each 1 g/d omega-3 fatty acids supplementation significantly improved depressive symptoms in adults with and without depression (moderate-certainty evidence), with a larger improvement in patients with existing depression. Dose-response analyses indicated a U shaped effect in patients with existing depression, with the greatest improvement at 1.5 g/d. The analysis showed that omega-3 fatty acid supplementation significantly increased depression remission by 19 more per 100 in patients with depression (low-certainty evidence). Supplementation with omega-3 fatty acids did not reduce the risk of developing depression among the general population, but it did improve the severity of depression among patients with existing depression.
... 14 Berbagai jenis penelitian mengenai omega 3 dan gangguan kesehatan mental juga sudah banyak diterbitkan di luar Indonesia. [15][16][17][18][19][20] (21)(22)(23) Kuesioner Depression Anxiety Stress Scale (DASS 42), untuk mengetahui adanya gangguan depresi dan/atau kecemasan yang dialami sampel penelitian. DASS, dikembangkan oleh Lovibond dan Lovibond tahun 1995 dan diusulkan oleh Australian Psychological Society, memiliki empat poin skala Likert, yang terdiri dari 42 item yang memeriksa tingkat depresi, kegelisahan, dan stres pada subjek eksperimen. ...
... Item skala kecemasan adalah 2,4,7,9,15,19,20,23,25,28,30,36,40,41. Item skala stres adalah 1,6,8,11,12,14,18,22,27,29,32,33,35,35,39. Kuesioner DASS 42 dibagikan kepada sampel pada waktu bersamaan dan dikerjakan bersamaan selama 10 menit. ...
Pendahuluan: Gangguan mental yang umum terjadi pada mahasiswa yaitu depresi dan kecemasan. Sejumlah penelitian menyebutkan bahwa asam lemak omega-3 memilikiefek pencegahan terhadap gangguan mental seperti depresi dan kecemasan pada remaja dandewasa awal. Tujuan: Penelitian ini bertujuan untuk mengetahui gambaran asupan omega 3dan kejadian Common Mental Disorders pada mahasiswa Ilmu Gizi Fakultas KesehatanMasyarakat Universitas Hasanuddin. Bahan dan Metode: Penelitian ini dilakukan padamahasiswa Ilmu Gizi Fakultas Kesehatan Masyarakat Universitas Hasanuddin angkatan2017-2019 (n = 138). Asupan omega-3 pada mahasiswa diukur menggunakan SemiQuantitative Food Frequency Questionnaire (SQ-FFQ), common mental disorders (CMDs)berupa depresi dan/atau kecemasan diukur menggunakan Depression, Anxiety, and StressScale (DASS) dan dianalisis deskriptif menggunakan SPSS. Hasil: Terdapat 103 mahasiswa(74,6%) dengan tingkat asupan harian omega-3 defisit. Mahasiswa yang mengalami CMDssebanyak 107 mahasiswa (77,5%) diantaranya 4 mahasiswa (2,9%) yang mengalami depresi,65 mahasiswa (47,1%) yang mengalami kecemasan, dan 38 mahasiswa (27,5%) mengalamikeduanya (depresi dan kecemasan). Dari total 103 mahasiswa dengan asupan omega-3 defisitterdapat 80 mahasiswa (58%) yang mengalami CMDs dan 23 mahasiswa (16,7%) yang tidakmengalami CMDs. Kesimpulan: Tingkat asupan omega-3 mahasiswa defisit jauh lebihtinggi daripada tingkat asupan baik dan tingginya kejadian common mental disorders padamahasiswa Ilmu Gizi Fakultas Kesehatan Masyarakat Universitas Hasanuddin. Diperlukantindakan lanjut untuk kejadian CMDs dan peningkatan asupan omega-3 pada mahasiswa.
... Around 85% of individuals with depression also experience significant symptoms of anxiety [4]. Mixed depressive and anxiety disorders were included in the depressive disorders chapter of the International Classification of Disease (ICD- 11), showing that both disorders could occur together. Previous research has shown that patients with major depressive disorder and significant anxiety in the STAR*D trial had lower remission rates, longer recovery times, increased side effects, and more severe adverse events, resulting in worse outcomes compared to those without anxiety [5]. ...
... At the same time, there has been much interest in whether interventions with n-3 PUFAs can prevent or alleviate anxiety. 12-week supplementation of n-3 PUFA was found to have the ability to reduce inflammation and anxiety among healthy young adults [11]. A systematic review revealed modest anxiolytic effects of n-3 PUFAs in individuals with anxiety symptoms [12]. ...
Purpose
Major depressive disorder (MDD) is frequently accompanied by the symptoms of clinical anxiety. Since our previous research has found that n-3 PUFA supplementation alleviates anxiety in MDD, this study was aimed to further explore whether n-3 PUFA supplementation improves anxiety symptoms in depression by directly manipulating fatty acid levels.
Methods
A secondary analysis of biomarker data (erythrocyte fatty acid composition) collected as part of the randomized clinical trial which investigated the adjunctive effect of n-3 PUFAs was conducted on 72 venlafaxine-treated outpatients with first-diagnosed, drug-naïve depression. All participants with longitudinal biomarker data were included in the association analysis to determine how n-3 PUFA supplementation influences fatty acid composition and alleviates anxiety symptoms in depression.
Results
Decreases of the C20:3n6 were found in all participants at both follow-up time points (χ² = 96.36, p = 0.000). The n-3 index (χ² = 10.59, p = 0.001), EPA (χ² = 24.31, p = 0.000), and C22:5n3/C20:5n3 ratio (χ² = 10.71, p = 0.001) were increased, while C22:4n6 (χ² = 7.703, p = 0.006) was decreased in n-3 PUFA group compared to the placebo group. The improvement in anxiety symptoms positively correlates with the extent of reduction of C16:0, C18:0, and total fatty acid levels as well as D5 desaturase activity (p < 0.05).
Conclusion
These data suggest that the anxiolytic effect exerted by n-3 PUFAs in first-diagnosed, drug-naïve depression is manipulated by erythrocyte fatty acid levels. Saturated fatty acid levels have an important role in predicting the severity of anxiety symptoms.
... 14 A previous study suggested that a high ꞷ-6 to ꞷ-3 PUFA ratio could increase the risk of depression. 19 Increased ꞷ-6/ꞷ-3 was associated with significant depression and increased production of proinflammatory cytokines in students, according to a randomized controlled experiment. This study discovered that lowering the ꞷ-6/ꞷ-3 ratio decreased anxiety and encouraged decreases in IL-6 and TNF-α production, as well as minor variations in serum TNFα. ...
... This study discovered that lowering the ꞷ-6/ꞷ-3 ratio decreased anxiety and encouraged decreases in IL-6 and TNF-α production, as well as minor variations in serum TNFα. 19 A study conducted by Thesing, et al. (2020) found no protective benefit for major depression disorder (MDD) recurrence from high levels of ꞷ-3 PUFA, DHA, EPA, low ꞷ-6 PUFA levels, or a high ꞷ-3/ꞷ-6 PUFA ratio in MDD patients who recovered for a maximum of eight years of follow-up. 20 A study by Matsuoka, et al. (2017) on fish diet, consumption of ꞷ-3 PUFAs, and risk of depression in Japan discovered no statistically significant correlation between the ratio of ꞷ-6 and ꞷ-3 and depression risk. ...
Introduction: Depression affects 45.19% of pulmonary tuberculosis (TB) patients' adherence to treatment, resulting in increased morbidity and death, medication resistance, and continued disease transmission. This study aimed to examine the relationship between omega-6/omega-3 (ꞷ-6/ꞷ-3) polyunsaturated fatty acids (PUFA) intake ratio and depression score in patients with pulmonary TB at Persahabatan National Respiratory Referral Hospital, Jakarta. Methods: This was a cross-sectional study of 99 subjects with pulmonary TB. Data were collected using the Semi-Quantitative Food Frequency Questionnaire (SQ-FFQ), anthropometric measurements, and the Beck Depression Inventory-II (BDI-II). Results: Correlation analysis used the Spearman test and revealed the ratio of ꞷ-6/ꞷ-3 PUFAs intake of 7.78 ± 1.13, the median value of depression score was 9 (10-36). There was no correlation between ꞷ-6/ꞷ-3 PUFA intake and depression score (r = 0.063; p = 0.534). Conclusion: There was no correlation between ꞷ-6/ꞷ-3 PUFAs intake ratio and depression scores in pulmonary TB patients. This is the first study to examine the correlation between ꞷ-6/ꞷ-3 PUFA intake ratio and depression score in pulmonary TB patients.
... First, we did not perform metabolomics analysis of rat fecal and blood samples to investigate the mechanism by which altered gut microbiota affects IBS via the MGBA. Second, IBS is associated with a high prevalence of psychological disorders, particularly depression and anxiety [49,50]. However, we did not investigate whether L. cremoris PS133 can improve depression or anxiety in rats with IBS-like symptoms. ...
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder marked by abdominal pain and irregular bowel habits. Recently, more and more evidence supports gut microbiota imbalance in IBS and highlights the potential of probiotics in restoring gut health and reducing symptoms. In this study, we explored the effects of Lactococcus cremoris PS133 (PS133) on an IBS-like condition in rats triggered by 5-hydroxytryptophan (5-HTP), a serotonin precursor. Eight-week-old Sprague Dawley rats received either PS133 or saline for 14 days, followed by 5-HTP to induce IBS-like symptoms. Colorectal distension tests showed that PS133 reduced visceral hypersensitivity. PS133 also protected intestinal mucin against 5-HTP-induced degradation, as seen in alcian blue staining, and increased the levels of tight junction proteins (occludin and zonula occludens-1) in the colon, indicating improved gut barrier integrity. Additionally, PS133 normalized the levels of substance P (a neuropeptide) in the spinal cord and altered 5-hydroxyindoleacetic acid (a serotonin metabolite) in the brain. Gut microbiota analysis revealed PS133 regulated specific bacterial groups, including [Eubacterium]_coprostanoligenes_group and Lactococcus. Overall, PS133 improved gut function, reduced IBS-like symptoms, and modulated gut microbiota, neurotransmitters, and intestinal barrier health in this IBS model.
... Randomize kontrollü bir çalışmada, omega-3 yağ asidi takviyesinin IL-6 üretimini azalttığı ve omega-6/omega-3 oranının azalmasının IL-6 ve TNF-α üretiminin azalmasıyla ilişkili olduğu rapor edilmiştir. 29 Başka bir çalışmada, omega-3 yağ asidi türevi olan koruyucu D1'in (protectin D1), viral replikasyonu azalttığı ve influenza enfeksiyonu sonrasında semptomları ve hayatta kalmayı iyileştirdiği belirlenmiştir. 30 Omega-3 suplementasyonunun HIV pozitif hastalarda inflamatuar belirteçlere etkisi ile ilgili bir meta analiz çalışmasında, ortalama 18 hafta boyunca 1,000-4,000 mg/gün arası omega-3 takviyesi (EPA+DHA) alanlar incelenmiştir. ...
ÖZET
Enfeksiyonlar, tedavilerdeki ilerlemelere rağmen hala ülke ekonomilerini olumsuz yönde etkileyen ve bireylerin, toplumların yaşantılarını tehlikeye atan önemli bir küresel sorundur. Beslenme, enfeksiyon ve enfeksiyon hastalıklarının oluşum mekanizması ile yakından ilişkilidir. Bu nedenle; bireylerin beslenme durumu enfeksiyonların şiddeti, remisyonu, insidansı üzerinde kritik öneme sahiptir. Yetersiz beslenme, enfeksiyon hastalıklarındaki yüksek morbidite ve mortalite oranlarının en önemli nedenlerinden birisidir. İnsan vücudu, vücut yapılarını korumak ve konak metabolizmasını uygun bir şekilde düzenlemek için enerji ve karbonhidrat, protein, yağ gibi makro besin ögelerine gereksinme duymaktadır. Diyet yağ miktarı ve yağ örüntüsünün, enfeksiyon ve inflamatuar süreç dahil olmak üzere birçok metabolik faaliyette rol oynadığı belirtilmiştir. Yağlar hücresel enerji kaynağı olmanın yanı sıra bağışıklık tepkilerini düzenleyen biyolojik moleküllerin sentezinde de rol oynamaktadır. Esansiyel yağ asitleri, özellikle omega-3 ve omega-6 yağ asitleri, inflamasyon ve bağışıklık tepkilerinin düzenlenmesinde kritik öneme sahiptir. Bu bölümde, enfeksiyonlarda yağlar ve yağ asitlerinin önemi incelenmiştir.
... Evidence suggests that supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which belong to the omega-3 PUFAs, may alleviate depression and anxiety symptoms [18,19]. Diets rich in PUFAs, such as the Mediterranean diet which is known for criteria met. ...
Purpose: Young adults experience high stress levels, leading to mood disorders. This study investigates the associations between specific fatty acid levels, lipid profiles, inflammatory markers, and emotional well-being among young adults.
Methods: Seventy-two young adults aged 18-35 participated in this study. Participants completed self-assessments of depression severity (PHQ-9), stress (PSS-10), insomnia (ISI), and anxiety (GAD-7). Blood samples were collected and analyzed for plasma fatty acid profiles, lipid profiles, C-reactive protein (CRP), and kynurenine pathway metabolites. Classification and Regression Tree(C&RT) and multivariate stepwise regression analyses were employed to identify potential predictors of mental health outcomes.
Results: The analyses revealed significant associations between certain fatty acids, lipid markers, and mental health conditions. Lauric acid, myristic acid, and eicosatrienoic acid were identified as potential indicators of mental health issues. Higher levels of palmitoleic acid were linked to increased depressive symptoms, while higher oleic acid levels were associated with reduced depression. Anxiety was influenced by myristoleic acid and docosahexaenoic acid. Stress and sleep disturbances correlated with specific fatty acids. The models explained a significant percentage of variability in mental health outcomes, accounting for 25% in both depressive symptoms and anxiety, 23% in stress, and 43% in sleep disturbances.
Conclusions: Specific fatty acids, associated with lipid profiles, kynurenic acid, and CRP, significantly impact the mental health of young adults. Monitoring biomarkers may assist in managing mental health disorders. Personalized dietary interventions could improve well-being and sleep quality. Further research is needed to confirm these findings and establish causal relationships.
Key words: young adults, sleep disturbances, mental health, fatty acids, KYNA.
... The metabolizing enzymes exhibit fluid pleomorphism, allowing them to adapt to any genetic modifications resulting from interactions between our genes and nutrition. All of this points to the possibility of customizing dietary therapies for depression management based on a person's genetic composition [88]. ...
Millions worldwide suffer from major depression, and recent studies have highlighted the effect of diet on mental health. However, research using nutritional genomics to create personalized diets for managing depression is still limited. This review explores the role of nutritional genomics in developing personalized dietary strategies for depression, focusing on key genetic markers. A comprehensive review of current literature, with a focus on studies that analyze the interplay between specific genes, nutrient intake, and depression was carried out. Databases like PubMed, Google Scholar, and Web of Science were searched using keywords like “nutritional genomics,” “personalized diets,” and “depression.” Relevant articles were also selected based on their contribution to how genetic variations affect dietary components linked to mental health. We identified several genetic markers such as SLC6A4 and BDNF that may influence how individuals with depression respond to specific nutrients, such as vitamin D, folate, and omega-3 fatty acids. These markers include variations in genes related to neurotransmitter pathways, inflammation, and neuroplasticity. This review highlights the potential of nutritional genomics as a tool for creating more individualized dietary plans for managing depression. With the use of genetic insights into dietary recommendations, healthcare providers could offer more targeted interventions.
... Initially, Jan found that Omega-3 supplementation lowered inflammation and anxiety in medical students during exam weeks [49]. ...
Dr. Janice Kiecolt-Glaser as an undergraduate obtained a major in psychology and a minor in biological sciences which was an early indication of her budding interest in how the brain talks to a variety of physiologic systems. Early in her research career Jan began to build a research team that eventually consisted of scientists with expertise in a variety of disciplines including virology, immunology, endocrinology, nutrition science, biostatistics, genetics, and the microbiome. Additionally, Jan enlisted the aid of a group of bright energetic pre- and post-doctoral graduate students, obtained numerous NIH grants, and utilized an excellent Clinical Research Center. Over many years Jan directed these teams to help with understanding some of the biologic consequences of common life stressors such as loneliness, academic examinations, marital discord, breast cancer survivorship, and dementia caregiving. In this survey of her accomplishments, I will present some of the highlights of her prolific contributions which have encouraged many to enter the field of psychoneuroimmunology.
... n-3 PUFA deficiency has been implicated in psychiatric disorders including schizophrenia, depression, and autism. Evidence also implicates adolescence as the most vulnerable period for the onset of majority of these psychiatric illnesses (Bondi et al., 2014;Kiecolt-Glaser et al., 2011). ...
This review provides a comprehensive analysis of the gut microbiota and its associated metabolites in relation to stress and anxiety disorders, with a specific focus on adolescents. It addresses the dearth of information regarding the composition of microbiota-associated metabolites that have the potential to effectively alleviate anxiety and stress disorders in this age group. Adolescence is a vulnerable period characterized by hormonal, physiological, emotional, and environmental changes, making individuals more prone to psychiatric disorders that manifest as stress and anxiety. However, treatment is challenging due to patient non-compliance, particularly in refractory cases, necessitating tailored interventions. The gut microbiota, a vast community of microorganisms residing in the gastrointestinal system, plays a crucial role in influencing brain function through the microbiota-gut-brain axis (MGBA). Understanding the role of the gut microbiota in stress and anxiety disorders has opened avenues for potential targeted and innovative therapeutic approaches. This review consolidates the existing knowledge about gut microbiota and associated metabolites implicated in stress and anxiety disorders in adolescents. Through an extensive literature review, we compile a comprehensive list of microorganisms and metabolites known to alleviate symptoms of these disorders. The identification of microbiota-associated metabolites with the potential to ameliorate stress and anxiety disorders in adolescents can bridge the knowledge deficit and contribute to the development of novel treatment strategies and interventions, including unconventional approaches such as fecal microbiota transplantation (FMT).
... During the time I was in her lab, Dr. Kiecolt-Glaser's studies focused on inflammation and cancer. Her work was on the cutting edge of establishing bi-directional relationships between depression and inflammation [12], understanding how psychosocial, lifestyle, and clinical factors impact stress reactivity and inflammatory responses [13,14] (including directions co-led with her mentees [15][16][17]), and testing how interventions could reduce chronic inflammation and cellular aging [6,18,19]. She encouraged my involvement in these directions [20,21], as well as complementary interests in cognitive function [7,22]. ...
Psychoneuroimmunology (PNI) researchers can advance their careers and increase their scientific impact by prioritizing their writing skills. In addition to Dr. Kiecolt-Glaser's landmark research that inspired this special issue, her legacy is reflected in her prolific writing. Dr. Kiecolt-Glaser has the unique ability to convey her innovative research clearly and to diverse audiences. She also made writing mentorship a critical part of the training experience in her lab. In these ways, Dr. Kiecolt-Glaser's writing skills and mentorship have shaped both the PNI field and her trainees' careers. In this paper, I distill lessons learned about writing from Dr. Kiecolt-Glaser during my time as a graduate student in her Stress and Health Lab in the 2010s. I reflect on Dr. Kiecolt-Glaser's influence on her trainees' writing habits, summarize “writing pearls” inspired by her feedback/revisions, and provide observations on her writing mentorship habits. These tips are intended to help PNI trainees to clearly communicate their work and to help mentors reflect on ways they can prioritize and advance their trainees' writing skills. Finally, I reflect on how Dr. Kiecolt-Glaser's mentorship and scientific accomplishments had a tremendous impact on my own career development.
... Omega-3 polyunsaturated fatty acids (n-3 PUFA) (67), provide cardiovascular protection (68), enhance memory function (69), improve anxiety, and reduce inflammatory markers (70). Increasing research has shown that n-3 PUFA, primarily EPA and DHA, are known to affect the structure and function of the skin (71). ...
Krill oil (KO), extracted from the Antarctic marine crustacean Euphausia superba, is a nutrient-dense substance that includes rich profiles of n-3 polyunsaturated fatty acids (n-3 PUFAs), phospholipids (PLs), astaxanthin (ASX), as well as vitamins A and E, minerals, and flavonoids. As a high-quality lipid resource, KO has been widely used as a dietary supplement for its health-protective properties in recent years. KO has various benefits, including antioxidative, anti-inflammatory, metabolic regulatory, neuroprotective, and gut microbiome modulatory effects. Especially, the antioxidant and anti-inflammatory effects make KO have potential in skin care applications. With increasing demands for natural skin anti-aging solutions, KO has emerged as a valuable nutraceutical in dermatology, showing potential for mitigating the effects of skin aging and enhancing overall skin health and vitality. This review provides an overview of existing studies on the beneficial impact of KO on the skin, exploring its functional roles and underlying mechanisms through which it contributes to dermatological health and disease management.
... Her research illuminated the profound effects of chronic stress on immune function. From caregivers of spouses living with dementia [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], to medical students during exams [21][22][23][24], to cancer survivors , married couples , and other populations, Jan's work verified that stress alters immune responses, leaving individuals more vulnerable to infections and diseases. Her work has underscored the importance of the mind-body connection, emphasizing that mental well-being directly influences physical health. ...
... 20,22,23 Research by Rutting S et al. 24 has shown that PUFAs can raise IL-6 levels in primary pulmonary fibroblasts. Similarly, Kiecolt-Glaser et al. 25 found that n-3 FA supplementation increased IL-6 blood levels in young men. Additionally, Grimble et al. 26 reported that children who were given 300 mg/day of n-3 PUFA for 12 weeks experienced an increase in pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), and the anti-inflammatory cytokines (IL-10). ...
Abstract
The aim of this study was to investigate the effects of supplementing unsaturated free fatty acids (n-3FA) on the levels of specific cytokines associated
with cytokine storm in the blood of 72 Jordanian individuals (both men and women) who had insufficient vitamin D. The study was conducted using a
randomized controlled design (RCT). Individuals eligible for the study were randomly assigned to either the n-3FA supplemented (intervention) group
or the non-supplemented (control) group. The intervention group received 1,000 mg of wild salmon and fish oil complex, which is equivalent to 300 mg
of n-3FA, for a duration of eight weeks, while the control group did not. Blood tests to assess tumor necrosis factor-α (TNF-α), lipid profile, and fasting
blood sugar were conducted at baseline and after ten weeks (with a two-week washout period). Additionally, interleukin-6 (IL-6), interleukin-1β (IL-1β),
and interleukin-10 (IL-10) levels were measured. Our research indicates that taking n-3FA supplements significantly raised IL-1 β, IL-6, and IL-10 levels
compared to their initial levels. However, TNF-α levels did not show any significant changes. The interesting results of this randomized controlled trial could
be due to a possible harmful effect of n-3FA supplementation during cytokine storms (CS), specifically on IL-6. Therefore, additional clinical studies are
needed in the target patients during cytokine storm to determine if this supplement could affect the treatment with IL-6 antagonists.
... Current studies suggest that the combined pathological mechanisms of anxiety and depression in CHD are linked to inflammatory factors, neurotransmitters, the hypothalamic-pituitaryadrenal (HPA) axis, endocrine markers, and high-sensitivity Creactive protein (hs-CRP) (4,5), where the inflammatory response is a critical component of the combined anxiety and depressive disorder episodes in coronary artery disease (6). The main components of omega-3 PUFAs include alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), which can only be consumed through food and cannot be generated by the human body, with deep-sea fish oil being its most important source, and whose antidepressant effect is linked to reduced production of pro-inflammatory cytokines (7), but also participate in neuromodulatory transmission and play a positive role in depression (8); Furthermore, it possesses cardioprotective properties, such as avoiding sudden cardiac death and ameliorating heart failure (9,10). Several trials have proven its efficacy in preventing cardiovascular disease and depression. ...
Objective
The evidence demonstrates that omega-3 polyunsaturated fatty acids (omega-3 PUFAs) protect the cardiovascular system and alleviate anxious or depressive situations. We conducted a meta-analysis to evaluate the effectiveness of omega-3 PUFAs in the treatment of anxiety or depressive states in patients with coronary artery disease.
Methods
This meta-analysis analyzed data from randomized controlled trials to determine the efficacy of omega-3 PUFAs alone or in combination with conventional psychotropic medications in coronary artery disease patients suffering from anxiety or depression. Primary outcomes included changes in depression scores, the Beck Anxiety Inventory (BAI) scores, and the omega-3 index.
Results
Included were 6 trials involving 2,570 participants. Compared to controls,omega-3 PUFAs did not improve depression or anxiety {depression: [SMD=0.09 (95% CI: -0.07, 0.26)], anxiety [BAI: SMD=0.07 (95% CI: -0.17, 0.32)]}; For the results of the subgroup analyses, analyzed by different types of depression scales, four studies used the HAMD scale [SMD=0.19 (95% CI: -0.20, 0.58)]; 5 studies used the BDI-II scale [SMD=0.01 (95% CI: -0.07, 0.09)], all of which indicated no decrease in depression scale scores; analyzed by different types of intervention, 3 studies used the omega-3 PUFAs group [SMD=0.24 (95% CI: -0.26, 0.74)]; 2 studies used sertraline + omega-3 PUFAs [SMD=-0.08 (95% CI: -0.46, 0.31)], and the omega-3 index was elevated [SMD=1.33 (95% CI: 0.18, 2.49)], suggesting that the body’s omega-3 content was indeed replenished but did not change the patient’s depressive state; analyzed by different courses of therapy, a 10-week course of therapy [SMD=0.02 (95% CI: -0.23, 0.26)] and a 12-week course of therapy [SMD=0.40 (95% CI: -0.40, 1.20)] both resulted in a lack of improvement in depressive symptoms.
Conclusion
According to the available evidence, omega-3 PUFAs do not alleviate anxiety or depression in coronary artery disease patients.
Systematic Review Registration
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023391259.
... With these collaborators, Dr. Kiecolt-Glaser branched out to different populationsmedical students [4,[8][9][10], dementia caregivers [11][12][13], cancer survivors [14,15], married couples [3,7,16,17]-using various stress paradigms to demonstrate for whom and to what extent stress affects immunological processes. Her research portfolio is wide-ranging, reflecting her insatiable curiosity and ability to develop oblique expertise through daily, focused reading. ...
Over the past several decades, psychoneuroimmunologists have uncovered key principles (e.g., social support and stress management) that can inform future research content and conduct. That is, psychoneuroimmunology (PNI) can inform how scientists from all disciplines engage in the scientific method in a more sustainable manner. Dr. Janice Kiecolt-Glaser, a PNI pioneer, recently ended her long and celebrated career. Her unique engagement in the scientific method, including her mentorship style, is worthy of closer examination. As her final graduate student, I observed Dr. Kiecolt-Glaser's science and mentorship style at their full maturity. Her scientific content, remarkable in its own right, is the subject of commentaries and accolades; yet, her scientific conduct – the foundation of her success and innovation – deserves further consideration. This article outlines ten research conduct principles that Dr. Kiecolt-Glaser explicitly and implicitly taught: (1) applying the literature to one's own health behaviors; (2) knowing and remembering “the why” behind the science; (3) developing and adhering to a vision; (4) creating a streamlined workflow; (5) embracing team science; (6) pursuing depth and breadth; (7) communicating ideas clearly; (8) engaging in a daily rhythm of science; (9) treating trainees like future primary investigators; and (10) working toward clinical meaningfulness. These principles correspond to PNI findings and account for her health and longevity as a scientist.
... In addition, study by Yokoi-Shimizu et al. (2012) documented that EPA and DHA are believed to modulate melatonin production that is crucial for sleep regulation. Dietary intake of EPA and DHA can also treat and prevent anxiety and depression among adults and thus enhance nervous and mental health (Appleton et al., 2015;Kiecolt-Glaser et al., 2011). EPA and DHA also benefit in counteracting the adverse effects of muscle atrophy and hasten neuromuscular adaptation (Jeromson et al., 2015;Ochi & Tsuchiya, 2018) that play an important role in preventing the pathological calcification in cancer tissue. ...
Mud crab (Scylla olivacea) is a valuable crustacean that has been consumed as nutritious foods for human body maintenance, delicacy tasting and for medicinal purposes. This study aimed to develop a novel mud crab extract processed through lactic acid fermentation. The objective is to compare the nutritional value, antioxidant properties and lipid profiling of mud crab muscles and hepatopancreas extract. Protein content in mud crab muscles extract (MCME) was significantly (p < .05) higher compared to the hepatopancreas. Lipids in MCME were significantly lower (3.36 ± 3.00%) (p < .05) than in hepatopancreas extract (HE) (14.75 ± 2.14%). Both eicosapentaenoic acid and docosahexaenoic acid content in MCME were relatively higher but not significantly (p > .05) different to HE. The DPPH-radical scavenging activity of both extracts was similar (p > .05). However, the ferric reducing antioxidant power in MCME was higher (p < .05) compared to HE. Therefore, MCME has the potential as an alternative natural antioxidant for healthy product.
... Nutritional psychiatry [6] is a growing field of study focusing on nutritional interventions as part of the prevention and treatment of mental disorders. Previous studies have focused on the association between individual nutrients and anxiety, like Gluten [7], omega-3 fatty acids [8,9], vitamin D [10,11], turmeric [12], etc. However, recent studies declared that dietary patterns provide a holistic and detailed view of these associations [13]. ...
Background: In the present study, we explored the association between major dietary patterns, odds, and severity of anxiety disorders, which has not been clarified to date.Methods: This case-control study was conducted on 85 patients who were group-matched by gender with 170 healthy subjects. Dietary intakes were evaluated applying a 147-item validated food frequency questionnaire (FFQ). Anthropometric data collection was accomplished based on precise clinical assessments. Major dietary patterns were identified using principal component analysis (PCA). Multivariate odds ratios (OR) with 95% confidence intervals (CI) were used to investigate the association of the identified dietary patterns with anxiety disorders. Multiple linear regression analysis was used to evaluate the association between the GAD-7 score and major dietary pattern scores.Results: Three major dietary patterns were derived through PCA labeled as 'healthy', 'Western', and 'Mixed'. Those in the top tertile of the healthy dietary pattern were less likely to have anxiety disorders (OR = 0.26; 95%CI: 0.10, 0.66), while no significant relationship was found between Western and mixed dietary patterns and the odds of anxiety disorders. The severity of anxiety disorders, assessed by the GAD-7 score, was reduced by higher adherence to healthy dietary pattern (P = 0.003), and increased by greater adherence to mixed (P = 0.002) and Western (P = 0.001) dietary patterns.Conclusion: We provided evidence demonstrating an inverse association of healthy dietary pattern with odds, and severity of anxiety disorders. Also, higher adherence to Western and mixed dietary patterns resulted in greater GAD-7 scores.
... Students were asked to record food intake, sleep quality, and physical activity. The experimental group was given fish oil supplements to help with their anxiety [42]. ...
Medical students experience anxiety at higher rates than the general public and many are uniquely affected by additional test anxiety throughout their medical education. Although test anxiety has been studied for decades, little evidence has been published suggesting interventions improve examination performance in medical education. Therefore, we set out to review the current literature to elucidate efforts so far and establish trends in research.
Databases searched included PubMed, EMBASE, PsychINFO, ERIC, SCOPUS, and CINAHL. English language articles published between 2010 and 2021 were loaded into a reference manager to screen out duplicate articles. During the full-text screen and data extraction phase, reference lists were also inspected to identify additional articles for inclusion in the study.
Of 883 studies identified, 860 were excluded resulting in 22 studies for extraction and analysis. First-year (n = 15) and second-year (n = 12) students were primarily tested. Less than 10 included third- or fourth-year students. Self-help and wellness interventions were employed, though interventions ranged from dog therapy to deep breathing techniques to fish oil supplementation. Test anxiety was evaluated using self-report questionnaires, such as the Westside Test Anxiety Scale, Beck Anxiety Inventory, and State-Trait Anxiety Inventory. None of the studies reported improved examination scores.
This review identifies a variety of measurement tools and interventions attempting to mitigate test anxiety. As far as improving examination performance, none of the interventions reported was successful. Further research addressing test anxiety that results in improved medical student academic performance should be conducted and also use established assessment tools.
... In the study, anxiety levels were measured in these students during different stress periods. It was found in the study that those students who received polyunsaturated fatty acids showed a reduction in the level of anxiety than the control group (Kiecolt-Glaser et al. 2011;Naidoo 2021). The omega-3 fatty acids produce a reduction in anxiety through neurochemical and anti-inflammatory mechanisms that affect the brain (Selhub et al. 2014). ...
Stress leads to several health complications. Stress results in poor dietary habits and poor dietary habits lead to stress. Thus, stress and diet go hand in hand. Stress, eating behaviors, diet, addiction to food, and dietary modifications are important concepts associated with the modern lifestyle. The relation of stress with diet is very important and good dietary modifications can help to beat stress. Food has a very significant effect on health and mood, and by eating a good diet, various physical and psychological problems can be countered. Food products like dietary fibers, vitamins, minerals, vegetables, fruits, etc. are very important to maintain good health. The key to long life and stress lies to a great extent in the diet and food we consume along with good eating behavior.
... The inflammatory hypothesis of LLD provides a new direction for treatment [195]. Studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) [196][197][198][199], omega-3 fatty acids [200][201][202], statins [203,204], cytokine inhibitors [205], corticosteroids [206,207], and minocycline [208][209][210] have significant antidepressant effects when used as adjunctive therapies. Infliximab monotherapy also demonstrates some antidepressant effects [211]. ...
The origins of late-life depression are multifaceted and remain challenging to fully understand. While the traditional monoamine neurotransmitter hypothesis provides some insights, it falls short in explaining the disease's onset and progression, leaving treatments often less than optimal. There is an emergent need to uncover new underlying mechanisms. Among these, the "inflammation hypothesis" has been gaining traction in scientific discussions regarding late-life depression. There is compelling evidence linking inflammation processes to the emergence of this form of depression. This review delves into the nuanced relationship between inflammation and late-life depression, emphasizing the pivotal role and implications of inflammation in its pathogenesis. Changes in Ca2+ homeostasis, cytokine levels, brain-derived neurotrophic factor (BDNF), white cell ratios, and the involvement of the NOD-, LRR-, and Pyrin domain-containing protein 3 (NLRP3) inflammasome have all been suggested as potential biomarkers that tie inflammation to late-life depression. Furthermore, factors such as aging-induced DNA damage, oxidative stress, mitochondrial impairments, disruptions in the hypothalamic-pituitary-adrenal axis, activated microglia and associated neuroinflammation, as well as the gut-brain axis dynamics, could serve as bridges between inflammation and depression. Deepening our understanding of these connections could usher in innovative anti-inflammatory treatments and strategies for late- life depression.
... The ω-3 FAs are regarded as physiologically active compounds (PAC) that play an essential function in the reduction of cholesterol, aid in the production of compounds with low inflammation activity and potent platelet aggregation inhibitors, which help in improving cardiovascular health by functioning against the compounds responsible for CVD. 8,9 Thus, bakery fats are enriched with these essential ω-3 FAs to develop a healthier bakery fat. The incorporation of polyunsaturated fatty acids (PUFAs), however, poses several challenges due to their poor oxidation stability, leading to development of off-flavors and rancidity in final products. ...
Bakery products have gained prominence in modern diets due to their convenience and accessibility, often serving as staple meals across diverse regions. However, the fats used in these products are rich in saturated fatty acids and often comprise trans fatty acids, which are considered as a major biomarker for non‐communicable diseases like cardiovascular disorders, obesity and diabetes. Additionally, these fats lack the essential omega‐3 fatty acids, which are widely known for their therapeutic benefits. They play a major role in lowering the risk of cardiovascular diseases, cancer and diabetes. Thus, there is need for incorporating these essential fatty acids into bakery fats. Nevertheless, fortifying food products with polyunsaturated fatty acids (PUFAs) poses several challenges due to their high susceptibility to oxidation. This oxidative deterioration leads to not only the formation of undesirable flavors, but also a loss of nutritional value in the final products. This review focuses on the development of healthier trans‐fat‐free bakery fat enriched with omega‐3 fatty acids and its effect on the physicochemical, functional, sensory and nutritional properties of bakery fats and products. Further, the role of various technologies like physical blending, enzymatic interesterification and encapsulation to improve the stability of PUFA‐rich bakery fat is discussed, where microencapsulation emerged as a novel and effective technology to enhance the stability and shelf life. By preventing deteriorative changes, microencapsulation ensures that the nutritional, physicochemical and sensory properties of food products remain intact. Novel modification methods like interesterification and microencapsulation used for developing PUFA‐rich bakery fats have a potential to address the health risks occurring due to consumption of bakery fat having higher amount of saturated and trans fatty acids. © 2023 Society of Chemical Industry.
... [13][14][15] To our knowledge, no other clinical trial has been conducted on the effect of n-3 supplementation on depression in the context of cancer. However, our results are consistent with those of Kiecolt-Glaser et al.'s RCTs conducted in medical students 45 and middle-aged and older adults 17 also having low levels of depression at baseline and using a similar dosage (2.5 g/day; 2085 mg EPA and 348 mg DHA). Together, this could suggest that our participants were not symptomatic enough for us to be able to detect a therapeutic effect (i.e., floor effect). ...
Background
In the general population, a higher omega‐3 polyunsaturated fatty acids intake is associated with lower levels of several psychological symptoms, especially depression. However, the existing evidence in cancer is equivocal.
Methods
This phase IIB double‐blind, placebo‐controlled trial was aimed at comparing the effects of eicosapentaenoic acid monoacylglyceride (MAG‐EPA) supplementation and high oleic acid sunflower oil (HOSO; placebo) on depression levels (primary outcome) and other symptoms (anxiety, fear of cancer recurrence, fatigue, insomnia, perceived cognitive impairments; secondary outcomes). Participants, recruited in a prostate cancer clinic, were randomized to MAG‐EPA (3.75 g daily; n = 65) or HOSO (3.75 g daily; n = 65) for 1 year post‐radical prostatectomy (RP), starting 4–10 weeks before surgery. Patients completed self‐report scales at baseline (before RP) and 3, 6, 9, and 12 months after: Hospital Anxiety and Depression Scale (HADS), Fear of Cancer Recurrence Inventory (FCRI), Insomnia Severity Index (ISI), Fatigue Symptom Inventory (FSI), and Functional Assessment of Cancer Therapy—Cognitive Function (FACT‐Cog).
Results
Analyses showed significant reductions in HADS‐depression, HADS‐anxiety, FCRI, ISI, FSI‐number of days, and FACT‐Cog‐impact scores over time. A significant group‐by‐time interaction was obtained on FACT‐Cog‐Impact scores only; yet, the temporal change was significant in HOSO patients only.
Conclusions
Several symptoms significantly decreased over time, mainly within the first months of the study. However, MAG‐EPA did not produce greater reductions than HOSO. Omega‐3 supplementation does not seem to improve psychological symptoms of men treated with RP.
... Ejemplos de factores ambientales involucrados en esta problemática son la abundancia de alimentos, bajo estatus socioeconómico y la cultura. Por otro lado, entre los factores comportamentales se encuentra una ingesta excesiva de calorías, patrones de alimentación inadecuados, estilos de vida sedentarios y la falta de sueño (Kadouh & Acosta, 2017;Kiecolt-Glaser et al., 2011). ...
Eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are two biologically active omega-3 polyunsaturated fatty acids (n-3 PUFA), acquired by nutrition and incorporated in cell membranes’ phospholipids, thus playing a crucial role in human health and homeostasis. Due to their potential cardioprotective, anti-inflammatory, and anti-arrhythmic actions, n-3 PUFA emerge as an interesting therapeutic option for cardiac surgery (CS) patients. The aim of this review was to assess the effects of perioperative administration of n-3 PUFA in CS patients. A comprehensive literature search was conducted in order to identify prospective cohort studies and randomized controlled trials (RCT) reporting on the perioperative effects of n-3 PUFA among adult patients undergoing CS. A total of 31 articles, published between 1995 and 2022, including 10 543 patients, met the inclusion criteria. There seems to be a beneficial effect of n-3 PUFA supplementation for arrhythmias such as in Postoperative Atrial Fibrillation (POAF), reduction of Intensive Care Unit Length of Stay (ICULOS) & Hospital Length of Stay (HLOS), reduction in postoperative ventilation time, in inotropic demand, in postoperative fatigue, as well as in overall morbidity and mortality. Moreover, n-3 PUFA increase antioxidant potential, attenuate oxidative stress and inflammation with subsequent significant reduction in myocardial ischemia/reperfusion (I/R) injury, thus promoting early metabolic recovery of the heart after elective CS leading to improved myocardial protection. They represent a readily available and cost-effective strategy that could improve the outcome of patients undergoing CS, by reducing the risks of serious cardiovascular adverse events (AE), both peri- and post-operatively.
The ketogenic diet (KD) has attracted attention in recent years for its potential anticancer effects. KD is a dietary structure of high fat, moderate protein, and extremely low carbohydrate content. Originally introduced as a treatment for epilepsy, KD has been widely applied in weight loss programs and the management of metabolic diseases. Previous studies have shown that KD can potentially inhibit the growth and spread of cancer by limiting energy supply to tumor cells, thereby inhibiting tumor angiogenesis, reducing oxidative stress in normal cells, and affecting cancer cell signaling and other processes. Moreover, KD has been shown to influence T-cell-mediated immune responses and inflammation by modulating the gut microbiota, enhance the efficacy of standard cancer treatments, and mitigate the complications of chemotherapy. However, controversies and uncertainties remain regarding the specific mechanisms and clinical effects of KD as an adjunctive therapy for cancer. Therefore, this review summarizes the existing research and explores the intricate relationships between KD and cancer treatment.
It is well-established that both communicable and non-communicable diseases present significant challenges to global healthcare. A substantial proportion, approximately 85%, of these diseases can be attributed to environmental factors. Consequently, adopting a healthy lifestyle can serve as a preventative measure for the majority of these ailments. Research conducted over the past few decades has provided valuable insights into the biological properties of various natural sources, including fruits, vegetables, spices, and millets, as well as their bioactive constituents, with the aim of improving human health. Numerous bioactive compounds, commonly referred to as nutraceuticals, have been isolated from these natural sources. Compounds such as curcumin, piperine, resveratrol, isothiocyanates, epigallocatechin gallate (EGCG), quercetin, sulphoraphane, among others, have demonstrated significant disease-preventive and therapeutic properties against a wide spectrum of human ailments. These assertions are supported by extensive preclinical and clinical studies. Consequently, these nutraceutical agents hold immense potential for the prevention and treatment of diseases. Therefore, the present chapter aims to explain the significance of select nutraceuticals and their applications in promoting human well-being.
Background
Mental health disorders including major depressive disorder (MDD) are well recognized as major contributors to the global burden of disease among adolescents. The prevalence of adolescent depression is estimated to have increased by at least 25% during the COVID‐19 pandemic, compounding the already challenging problem of insufficient mental health service and service accessibility that existed prepandemic.
Omega‐3 polyunsaturated fatty acid (PUFA) supplementation is currently recommended as a preventive treatment for depression in high‐risk adults as well as a second‐line monotherapy for adults with mild to moderate MDD, and adjunctive to antidepressants for adults with moderate to severe MDD. The benefits of omega‐3 PUFA intake on depressive illness have been hypothesized to occur as a result of their effect on neurotransmission, maintenance of membrane fluidity, and anti‐inflammatory action. A comprehensive synthesis and quantification of the existing evidence on omega‐3 PUFA's efficacy in treating depression among children and adolescents is essential for clinicians to provide informed guidance to young people and their families, especially considering the absence of current guidelines for this age group.
Objectives
Primary objective
To determine the impact of omega‐3 PUFA supplementation versus a comparator (e.g. placebo, wait list controls, no treatment/supplementation, or standard care) on clinician‐diagnosed depression or self‐reported depression symptoms in children and adolescents.
Secondary objectives
To estimate the size of the effect of omega‐3 PUFAs on depression symptoms.
To estimate the effect of each type of omega‐3 PUFA (EPA or DHA), compared with placebo, on depression.
To determine if the effect is modified by dosage, format (capsule or liquid), sex, or age.
To determine compliance and attrition for omega‐3 PUFAs as an intervention for depression in children and adolescents.
To determine the safety of omega‐3 PUFAs as an intervention for depression in children and adolescents.
Search methods
We searched CENTRAL, MEDLINE, Embase, three other databases, reference lists of included studies, grey literature, and relevant reviews. The latest search date was 18 May 2023.
Selection criteria
We included randomized controlled trials (RCTs) involving males and females aged 19 years or younger with diagnosed depression comparing omega‐3 PUFA supplementation to placebo, wait list control, no treatment/supplementation, or standard care.
Data collection and analysis
We used standard Cochrane methods. Our primary outcomes were self‐reported depression symptoms and clinically diagnosed resolution of depression. Our secondary outcomes were attrition, adverse effects, and compliance with the intervention. We used GRADE to assess the certainty of evidence for key outcomes.
Main results
We included five trials with 228 participants in our meta‐analysis. All trials used a placebo comparator; intervention duration ranged from 10 to 16 weeks (median: 12 weeks).
Omega‐3 PUFA supplementation compared to placebo may reduce self‐reported depression symptoms, but the evidence is very uncertain (standardized mean difference [SMD] −0.34, 95% confidence interval [CI] −0.85 to 0.17; lower SMD means greater improvement in depression due to omega‐3 PUFA; 5 trials, 185 participants; very low‐certainty evidence).
Omega‐3 PUFA supplementation may have little to no effect on remission of depression symptoms compared to placebo, but the evidence is very uncertain (omega‐3 PUFA versus placebo: 50% versus 48%; odds ratio [OR] 1.11, 95% CI 0.45 to 2.75; 4 trials, 127 participants; very low‐certainty evidence).
Omega‐3 PUFA supplementation may result in little to no difference in attrition (dropouts) compared to placebo (omega‐3 PUFA versus placebo: 18% versus 19%; OR 0.94, 95% CI 0.46 to 1.90; 5 trials, 228 participants; low‐certainty evidence).
Omega‐3 PUFA supplementation may result in little to no difference in adverse effects, with one study reporting more muscle cramps in the fish oil group (13/27 participants) compared to the placebo group (6/29 participants); one study reported more frequent defecation in the omega‐3 group (1/29 participants) and one study identified mild skin rash and unusual/manic behavior in the placebo group (2/27 participants).
None of the included studies reported serious adverse effects.
Authors' conclusions
Based on five small studies, omega‐3 PUFA supplementation may reduce self‐reported depression symptoms, but the evidence is very uncertain. Omega‐3 PUFA supplementation may have little to no effect on depression remission compared to placebo, but the evidence is very uncertain. Omega‐3 PUFA supplementation may result in little to no difference in attrition or adverse effects. The studies observed no serious adverse effects.
This review highlights early‐stage research on omega‐3 PUFA and depression in young people. The evidence on the effects of omega‐3 PUFA supplementation in improving self‐reported depression symptoms or achieving depression remission in children and adolescents is very uncertain. While no harms are evident, more data are needed to confirm potential risks.
Addressing current limitations in the evidence base through the design and conduct of methodologically rigorous studies — larger sample sizes, varied dosages, eicosapentaenoic acid/docosahexaenoic acid ratios, treatment durations, and safety profiles — is crucial to advance our understanding of the role of omega‐3 PUFA supplementation for depression in children and adolescents.
Objectives: This study investigated the association between eating habits and the utilization of dietary supplements (DSs) according to food-related lifestyle (FRL) among Korean adults. Methods: This study included a total of 300 participants (150 men and 150 women) in their 20s to 60s living in Seoul and Gyeonggi Province. We identified two groups by factor and cluster analysis: an ‘active pursuit’ group and a ‘passive pursuit’ group. Differences in eating habits and DS utilization between the two groups were analyzed by chi-square test and t-test. Logistic regression analysis was used to analyze the effect of variables on DS consumption according to FRL. Results: There were significant differences between the two groups in terms of age, alcohol drinking frequency, total dietary score, change in DS consumption after coronavirus disease 2019, and current DS consumption (P < 0.05). The proportion who perceived many health benefits of DSs was higher in the ‘active pursuit’ group than in the ‘passive pursuit’ group (P = 0.003). The most commonly consumed type of DSs was multivitamins & minerals for the ‘active pursuit’ group, and omega-3 fatty acids for the ‘passive pursuit’ group. The ‘an active pursuit’ group consumed DSs 2.93 times more (95% confidence interval [CI]: 1.44–5.97) compared to the ‘passive pursuit’ group, after adjusting for confounders. In the ‘active pursuit’ group, the health pursuit (odds ratio [OR] = 6.54, 95% CI: 1.44– 29.61) and rational consumption pursuit factors (OR = 0.26, 95% CI: 0.08–0.83) were associated with DS consumption, whereas only the health pursuit factor had a significant association (OR = 5.37, 95% CI: 2.08–13.88) within the ‘passive pursuit’ group. However, total dietary score and DSs consumption did not show a relationship. Conclusions: By understanding the consumption characteristics of DSs according to FRL, this can serve as basic data necessary for promoting health through the utilization of DSs and healthy behaviors.
Abstract: This monograph aims to evaluate the utility of single nutraceuticals as well as whole dietary
interventions in the prevention and treatment of mental disorders. There is lot of data on the possible
advantages of prophylactic nutrition interventions for neurodegenerative diseases, most commonly
based on polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA), B vitamins. However,
there is little evidence for the treatment efficacy of these nutraceuticals for neurocognitive disorders so
far. Regarding patients at risk for schizophrenia or suffering from psychosis there is some evidence for
efficacy of N-acetylcysteine, PUFA, or B vitamins. The use of vitamin C, E, D3 or zinc in this population is
of uncertain utility. The supplementation of omega-3 PUFA, magnesium, zinc, selenium, iron or N
acetylcysteine is under investigation as prevention or treatment for depression and anxiety. Next, PUFA
omega-3, N-acetylcysteine, folic acid, coenzyme Q10, magnesium, or amino acids may be used in the
treatment of bipolar disorder. Nonetheless, their therapeutic role in the clinical population needs to be
confirmed. Recently, awareness of the influence of the gut microbiota, the central nervous system
functioning, and mental health has been growing. The imbalance of gut microbes and their dysfunction
has been shown to be connected with many mental disorders, e.g., schizophrenia, depression, autism
spectrum disorder, or bipolar disorder. There is research data on the influence of probiotics or prebiotics
for the functioning of the nervous system. Gut microbiota may also affect the metabolism of many
pharmaceuticals. On the other hand, animal studies have shown the influence of pharmacotherapy on the
microbiota changes. Regarding the whole dietary interventions, there is lack of consensus on the influence
of vegetarian or vegan diet on mood, stress level, or quality of life. Ketogenic diet, on the contrary, may
be an important part in the therapy of such diseases as binge eating disorder, autism spectrum disorder,
or schizophrenia. Additionally, it was shown that elimination of gluten from the diet may have favourable
effect on schizophrenia clinical picture. Moreover, Mediterranean diet, thanks to modulation of
inflammatory or metabolic processes, or the positive influence on cognitive functions, may be a
therapeutic option for patients with affective and psychotics disorders, among others. The same probably
applies to Japanese, Nordic o any other traditional diets. To sum up, dietary interventions are modern
preventive and therapeutic approaches to mental illnesses. Diet impacts the gut microbiota, modulating
metabolism and functioning of the host. Particular elements of the diet, like vitamins, macro- and
microelements, PUFA, influence on the metabolism of neurotransmitters, or may act as anti
inflammatory, immunomodulatory and antioxidant factors.
Keywords: mental disorders, mental illnesses, depression, nutrition, diet, dietary supplements,
nutraceuticals, vitamins, minerals, microbiota
Anxiety disorders disproportionally affect females and are frequently comorbid with eating disorders. With the emerging field of nutritional psychiatry, focus has been put on the impact of diet quality in anxiety pathophysiology and gut microbiome underlying mechanisms. While the relationship between diet and anxiety is bidirectional, improving dietary habits could better facilitate the actions of pharmacological and psychological therapies, or prevent their use. A better understanding of how gut bacteria mediate and moderate such relationship could further contribute to develop personalized programs and inform probiotics and prebiotics manufacturing. To date, studies that look simultaneously at diet, the gut microbiome, and anxiety are missing as only pairwise relationships among them have been investigated. Therefore, this study aims at summarizing and integrating the existing knowledge on the dietary effects on anxiety with focus on gut microbiome. Findings on the effects of diet on anxiety are critically summarized and reinterpreted in relation to findings on (i) the effects of diet on the gut microbiome composition, and (ii) the associations between the abundance of certain gut bacteria and anxiety. This novel interpretation suggests a theoretical model where the relationship between diet and anxiety is mediated and/or modulated by the gut microbiome through multiple mechanisms. In parallel, this study critically evaluates methodologies employed in the nutritional field to investigate the effects of diet on anxiety highlighting a lack of systematic operationalization and assessment strategies. Therefore, it ultimately proposes a novel evidence-based approach that can enhance studies validity, reliability, systematicity, and translation to clinical and community settings.
Objective
To conduct an overview of systematic reviews that explore the effectiveness of interventions to enhance medical student well-being.
Design
Overview of systematic reviews.
Data sources
The Cochrane Library of Systematic Reviews, MEDLINE, APA PsychInfo, CINAHL and Scopus were searched from database inception until 31 May 2023 to identify systematic reviews of interventions to enhance medical student well-being. Ancestry searching and citation chasing were also conducted.
Data extraction and synthesis
The Assessing the Methodological Quality of Systematic Reviews V.2 tool was used to appraise the quality of the included reviews. A narrative synthesis was conducted, and the evidence of effectiveness for each intervention was rated.
Results
13 reviews (with 94 independent studies and 17 616 students) were included. The reviews covered individual-level and curriculum-level interventions. Individual interventions included mindfulness (n=12), hypnosis (n=6), mental health programmes (n=7), yoga (n=4), cognitive and behavioural interventions (n=1), mind-sound technology (n=1), music-based interventions (n=1), omega-3 supplementation (n=1), electroacupuncture (n=1) and osteopathic manipulative treatment (n=1). The curriculum-level interventions included pass/fail grading (n=4), problem-based curriculum (n=2) and multicomponent curriculum reform (n=2). Most interventions were not supported by sufficient evidence to establish effectiveness. Eleven reviews were rated as having ‘critically low’ quality, and two reviews were rated as having ‘low’ quality.
Conclusions
Individual-level interventions (mindfulness and mental health programmes) and curriculum-level interventions (pass/fail grading) can improve medical student well-being. These conclusions should be tempered by the low quality of the evidence. Further high-quality research is required to explore additional effective interventions to enhance medical student well-being and the most efficient ways to implement and combine these for maximum benefit.
Depression is a multifactorial disease with unknown etiology affecting globally. It’s the second most significant reason for infirmity in 2020, affecting about 50 million people worldwide, with 80% living in developing nations. Recently, a surge in depression research has been witnessed, resulting in a multitude of emerging techniques developed for prediction, evaluation, detection, classification, localization, and treatment. The main purpose of this study is to determine the volume of depression research conducted on different aspects such as genetics, proteins, hormones, oxidative stress, inflammation, mitochondrial dysfunction, and associations with other mental disorders like anxiety and stress using traditional and medical intelligence (medical with AI). In addition, it also designs a comprehensive survey on detection, treatment planning, and genetic predisposition, along with future recommendations. This work is designed through different methods, including a systematic mapping process, literature review, and network visualization. In addition, we also used VOSviewer software and some authentic databases such as Google Scholar, Scopus, PubMed, and Web of Science for data collection, analysis, and designing comprehensive picture of the study. We analyzed 60 articles related to medical intelligence, including 47 from machine learning with 513,767 subjects (mean ± SD = 10,931.212 ± 35,624.372) and 13 from deep learning with 37,917 subjects (mean ± SD = 3159.75 ± 6285.57). Additionally, we also found that stressors impact the brain's cognitive and autonomic functioning, resulting in increased production of catecholamine, decreased cholinergic and glucocorticoid activity, with increased cortisol. These factors lead to chronic inflammation and hinder the brain's normal functioning, leading to depression, anxiety, and cardiovascular disorders. In the brain, reactive oxygen species (ROS) production is increased by IL-6 stimulation and mitochondrial cytochrome c oxidase is inhibited by nitric oxide, a potent inhibitor. Proteins, lipids, oxidative phosphorylation enzymes, and mtDNA are further disposed to oxidative impairment in the mitochondria. Consequently, mitochondrial dysfunction exacerbates oxidative stress, impairs mitochondrial DNA (mtDNA) or deletions of mtDNA, increases intracellular Ca2+ levels, changes in fission/fusion and mitochondrial morphology, and lastly leads to neuronal death. This study highlights the multidisciplinary approaches to depression with different aspects using traditional and medical intelligence. It will open a new way for depression research through new emerging technologies.
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Important sex-related differences have been observed in the onset, prevalence, and clinical phenotype of depression, based on several epidemiological studies. Social, behavioural, and educational factors have a great role in underlying this bias; however, also several biological factors are extensively involved. Indeed, sexually dimorphic biological systems might represent the underlying ground for these disparities, including cerebral structures and neural correlates, reproductive hormones, stress response pathways, the immune system and inflammatory reaction, metabolism, and fat distribution. Furthermore, in this perspective, it is also important to consider and focus the attention on specific ages and life stages of individuals: indeed, women experience during their life specific periods of reproductive transitional phases, which are not found in men, that represent windows of particular psychological vulnerability. In addition to these, other biologically related risk factors, including the occurrence of sleep disturbances and the exposure to childhood trauma, which are found to differentially affect men and women, are also putative underlying mechanisms of the clinical bias of depression. Overall, by taking into account major differences which characterize men and women it might be possible to improve the diagnostic process, as well as treat more efficiently depressed individuals, based on a more personalized medicine and research.
Omega-3 fatty acids, including alpha-linolenic acids (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have shown major health benefits, but the human body’s inability to synthesize them has led to the necessity of dietary intake of the products. The omega-3 fatty acid market has grown significantly, with a global market from an estimated USD 2.10 billion in 2020 to a predicted nearly USD 3.61 billion in 2028. However, obtaining a sufficient supply of high-quality and stable omega-3 fatty acids can be challenging. Currently, fish oil serves as the primary source of omega-3 fatty acids in the market, but it has several drawbacks, including high cost, inconsistent product quality, and major uncertainties in its sustainability and ecological impact. Other significant sources of omega-3 fatty acids include plants and microalgae fermentation, but they face similar challenges in reducing manufacturing costs and improving product quality and sustainability. With the advances in synthetic biology, biotechnological production of omega-3 fatty acids via engineered microbial cell factories still offers the best solution to provide a more stable, sustainable, and affordable source of omega-3 fatty acids by overcoming the major issues associated with conventional sources. This review summarizes the current status, key challenges, and future perspectives for the biotechnological production of major omega-3 fatty acids.
Stress has been well-documented to have a significant role in the etiopathogenesis of bruxism. Activation of the hypothalamic-pituitary-adrenal axis (HPA) and subsequent release of corticosteroids lead to increased muscle activity. Neurological studies have demonstrated that chronic stress exposure induces neurodegeneration of important neuronal structures and destabilization of the mesocortical dopaminergic pathway. These disruptions impair the abilities to counteract the overactivity of the HPA axis and disinhibit involuntary muscle activity, while at the same time, there is activation of the amygdala. Recent evidence shows that overactivation of the amygdala under stressful stimuli causes rhythmic jaw muscle activity by over activating the mesencephalic and motor trigeminal nuclei. The present review aimed to discuss the negative effects of certain vitamin and mineral deficiencies, such as vitamin D, magnesium, and omega-3 fatty acids, on the central nervous system. It provides evidence on how such insufficiencies may increase stress sensitivity and neuromuscular excitability and thereby reduce the ability to effectively respond to the overactivation of the sympathetic nervous system, and also how stress can in turn lead to these insufficiencies. Finally, the positive effects of individualized supplementation are discussed in the context of diminishing anxiety and oxidative stress, neuroprotection and in the reversal of neurodegeneration, and also in alleviating/reducing neuromuscular symptoms.
The development of a 21-item self-report inventory for measuring the severity of anxiety in psychiatric populations is described. The initial item pool of 86 items was drawn from three preexisting scales: the Anxiety Checklist, the Physician’s Desk Reference Checklist, and the Situational Anxiety Checklist. A series of analyses was used to reduce the item pool. The resulting Beck Anxiety Inventory (BAI) is a 21-item scale that showed high internal consistency (α = .92) and test—retest reliability over 1 week, r (81) = .75. The BAI discriminated anxious diagnostic groups (panic disorder, generalized anxiety disorder, etc.) from nonanxious diagnostic groups (major depression, dysthymic disorder, etc). In addition, the BAI was moderately correlated with the revised Hamilton Anxiety Rating Scale, r (150) = .51, and was only mildly correlated with the revised Hamilton Depression Rating Scale, r (153) = .25.
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.
The repeatability of a risk factor measurement affects the ability to accurately ascertain its association with a specific outcome. Choline is involved in methylation of homocysteine, a putative risk factor for cardiovascular disease, to methionine through a betaine-dependent pathway (one-carbon metabolism). It is unknown whether dietary intake of choline meets the recommended Adequate Intake (AI) proposed for choline (550 mg/day for men and 425 mg/day for women). The Estimated Average Requirement (EAR) remains to be established in population settings. Our objectives were to ascertain the reliability of choline and related nutrients (folate and methionine) intakes assessed with a brief food frequency questionnaire (FFQ) and to estimate dietary intake of choline and betaine in a bi-ethnic population.
We estimated the FFQ dietary instrument reliability for the Atherosclerosis Risk in Communities (ARIC) study and the measurement error for choline and related nutrients from a stratified random sample of the ARIC study participants at the second visit, 1990-92 (N = 1,004). In ARIC, a population-based cohort of 15,792 men and women aged 45-64 years (1987-89) recruited at four locales in the U.S., diet was assessed in 15,706 baseline study participants using a version of the Willett 61-item FFQ, expanded to include some ethnic foods. Intraindividual variability for choline, folate and methionine were estimated using mixed models regression.
Measurement error was substantial for the nutrients considered. The reliability coefficients were 0.50 for choline (0.50 for choline plus betaine), 0.53 for folate, 0.48 for methionine and 0.43 for total energy intake. In the ARIC population, the median and the 75th percentile of dietary choline intake were 284 mg/day and 367 mg/day, respectively. 94% of men and 89% of women had an intake of choline below that proposed as AI. African Americans had a lower dietary intake of choline in both genders.
The three-year reliability of reported dietary intake was similar for choline and related nutrients, in the range as that published in the literature for other micronutrients. Using a brief FFQ to estimate intake, the majority of individuals in the ARIC cohort had an intake of choline below the values proposed as AI.
We explored the expression of the interleukin 2 receptor (IL-2R) and the synthesis of IL-2R messenger RNA by peripheral blood leukocytes obtained from medical students experiencing examination stress in three independent studies. The peripheral blood leukocytes obtained at low-stress baseline periods had significantly higher percentages of IL-2R-positive cells when compared with cells obtained from the same individuals during examinations. In addition, IL2-R messenger RNA in peripheral blood leukocytes decreased significantly during examination periods in a subset of 13 subjects. In one study, we found an increase in the accumulation of interleukin 2 in cultures of cells showing down regulation of IL-2R expression and IL-2R messenger RNA levels. While there are ample data demonstrating stress-associated decrements in the immune response in humans and animals, these data provide the first evidence that this interaction may be observed at the level of gene expression. The data suggest one mechanism whereby the central nervous system modulates the immune response during psychological stress.
Eskimos living in rural southwestern Alaska depend on fish and marine mammals as major sources of subsistence food. Fatty acid concentrations in 80 Yupik Eskimos living in either a coastal or river village of southwestern Alaska were compared with those of non-Native control subjects. Concentrations of total plasma omega-3 fatty acids, eicosapentaenoic acid (20:5 omega-3), and docosahexaenoic acid (22:6 omega-3) were 4.3, 13, and 6.8 times higher, respectively, in Native participants than in non-Native control subjects. Concentrations of these fatty acids were higher in coastal-village than in river-village participants; concentrations paralleled consumption of marine mammal oil and marine fish. The ratios of eicosapentaenoic to arachidonic acid for adult coastal- and river-village participants were 1.16 and 0.70, respectively, 14 and 9 times those of non-Native adults, respectively. There was no increase in the mean bleeding times of Native participants of either village.
Fish contains high concentrations of omega-3 polyunsaturated fatty acids. Several studies have reported depletions of omega-3 fats among depressed patients, and a cross-national comparison has revealed a significant inverse correlation between annual prevalence of major depression and fish consumption. In a sample of 3,204 Finnish adults, depressive symptoms were estimated with the Beck Depression Inventory. A frequency question was used to measure fish consumption. Multiple logistic regression analysis was conducted to assess the association between depression and fish consumption. After the analysis adjusted for potential confounders, the likelihood of having depressive symptoms was significantly higher among infrequent fish consumers than among frequent consumers.
This book contains 18 chapters discussing the roles of specific nutrients in maintaining the immune response and protection against infection and non-communicable diseases, and the influence of various factors, such as exercise and aging, on the interaction between nutrition and immune function. The contents include methods for studying nutrient-immune function interactions, the impact of undernutrition on immune function and infection, the influences of fatty acids, amino acids, antioxidant vitamins, various minerals and probiotics on immunity, food allergies, immunological effects of changes throughout the life cycle, and public health policy implications.
Four methylation methods were evaluated for use in the gas chromatographic (GC) quantitation of conjugated linoleic acid (CLA) isomers, which are potential anticarcinogen. The methods were (1) sodium methoxide in methanol (NaOMe-MeOH), (2) American Oil Chemists' Society (AOCS) procedure Ce 2-66, which involves methanolic sodium hydroxide followed by boron trifluoride in methanol, (3) tetramethylguanidine in methanol (TMG-MeOH), and (4) direct transesterification with methanolbenzene- acetyl chloride (DAC). Purified methyl esters of isomerized linoleic acid containing 86% CLA isomers were methylated and analyzed by GC. The AOCS and DAC methods resulted in 3 and 50% losses in cis-9,trans-11-octadecadienoic acid (9c, 111 CLA isomer) and trans-10,cis-12 octadecadienoic acid (10t, 12c CLA isomers), respectively. Compared with the control, the AOCS and DAC methods increased the yield of the trans,trans CLA isomers (trans-9,trans-11- and trans-10, trans-12-octadecadienoic acid) by 1.07-fold and a 10-fold, respectively. A non-CLA artifact that eluted close to CLA peaks was formed during methylation by the AOCS and DAC methods. Thus, the DAC and AOCS methods are not suitable for quantitation of CLA isomers. The NaOMe-MeOH and TMG-MeOH methods, however, are suitable for quantitation of CLA isomers in fats containing low concentrations of free fatty acids.
Lipid decomposition studies in frozen fish have led to the development of a simple and rapid method for the extraction and purification of lipids from biological materials. The entire procedure can be carried out in approximately 10 minutes; it is efficient, reproducible, and free from deleterious manipulations. The wet tissue is homogenized with a mixture of chloroform and methanol in such proportions that a miscible system is formed with the water in the tissue. Dilution with chloroform and water separates the homogenate into two layers, the chloroform layer containing all the lipids and the methanolic layer containing all the non-lipids. A purified lipid extract is obtained merely by isolating the chloroform layer. The method has been applied to fish muscle and may easily be adapted to use with other tissues.
Studies which have investigated the influence of increased consumption of n-3 polyunsaturated fatty acids (PUFA) upon indices of immune function in healthy humans are reviewed. Four studies have investigated the effects of α-linolenic acid (ALNA; 2 to 18 g per day). Over 25 studies have investigated the effects of the long chain n-3 PUFA and these have used 0.55 to 14.4 g eicosapentaenoic acid (EPA) plus docosahexanoic acid (DHA) per day. Studies have been of 3 to 52 weeks duration. Most studies have examined the functions of immune cells ex vivo; there are a limited number of studies reporting in vivo measures of immune status/responses. High levels of either ALNA or EPA + DHA decrease chemotaxis of neutrophils and monocytes, production of reactive oxygen species by neutrophils and monocytes, production of pro-inflammatory cytokines by monocytes and T lymphocytes, and T lymphocyte proliferation. For most of these functions it is not possible to determine dose-response relationships because of experimental differences among studies. Thus, it is not clear what the level of n-3 PUFA required to exert the different effects is. The immunological effects of large amounts of n-3 PUFA suggest that they might be useful as therapies for diseases characterized by immune dysfunction. Evidence for beneficial effects of long chain n-3 PUFA in rheumatoid arthritis is strong and there is less strong evidence for benefit in Crohn’s disease, ulcerative colitis and psoriasis and among some adult asthmatics.
Background:
It has been hypothesized that depletion of cell membrane n3 polyunsaturated fatty acids (PUFA), particularly docosahexanoic acid (DHA), may be of etiological importance in depression.
Methods:
We measured the fatty acid composition of phospholipid in cell membranes from red blood cells (RBC) of 15 depressive patients and 15 healthy control subjects.
Results:
Depressive patients showed significant depletions of total n3 PUFA and particularly DHA. Incubation of RBC from control subjects with hydrogen peroxide abolished all significant differences between patients and controls.
Conclusions:
These findings suggest that RBC membranes in depressive patients show evidence of oxidative damage. Possible interpretations, and implications for the etiology and treatment of depression, are discussed.
Depression during pregnancy has adverse consequences for both mother and child. Although common in western countries, depression appears to be virtually absent in countries with high seafood intake. We test the hypothesis that low seafood intake during pregnancy is associated with increased prevalence of depressive symptoms.
This study used data prospectively collected from women participating in the Avon Longitudinal Study of Parents and Children in the period 1991-1992. At 32 weeks' gestation, the mother completed a questionnaire that included symptoms of depression and a food frequency questionnaire from which the amount of omega-3 fatty acids from fish was calculated. Statistical analysis took social and lifestyle factors into account.
Unadjusted and adjusted analyses showed lower maternal intake of omega-3 from seafood was associated with high levels of depressive symptoms. Compared with women consuming more than 1.5 g omega-3 from seafood per week, those consuming none were more likely to have high levels of depressive symptoms at 32 weeks' gestation (adjusted odds ratios = 1.54; 95% confidence interval = 1.25-1.89).
These observational data support an association between low omega-3 intake from seafood and increased risk of high levels of depressive symptoms during pregnancy. Eating seafood during pregnancy may have beneficial effects on mental well-being.
The CES-D scale is a short self-report scale designed to measure depressive symptomatology in the general population. The items of the scale are symptoms associated with depression which have been used in previously validated longer scales. The new scale was tested in household interview surveys and in psychiatric settings. It was found to have very high internal consistency and adequate test- retest repeatability. Validity was established by pat terns of correlations with other self-report measures, by correlations with clinical ratings of depression, and by relationships with other variables which support its construct validity. Reliability, validity, and factor structure were similar across a wide variety of demographic characteristics in the general population samples tested. The scale should be a useful tool for epidemiologic studies of de pression.
Some prospective studies have shown an inverse association between fish intake and risk of stroke, but none has examined the relationship of fish and omega-3 polyunsaturated fatty acid intake with risk of specific stroke subtypes.
To examine the association between fish and omega-3 polyunsaturated fatty acid intake and risk of stroke subtypes in women.
Prospective cohort study of women in the Nurses' Health Study cohort, aged 34 to 59 years in 1980, who were free from prior diagnosed cardiovascular disease, cancer, and history of diabetes and hypercholesterolemia and who completed a food frequency questionnaire including consumption of fish and other frequently eaten foods. The 79 839 women who met our eligibility criteria were followed up for 14 years.
Relative risk of stroke in 1980-1994 compared by category of fish intake and quintile of omega-3 polyunsaturated fatty acid intake.
After 1 086 261 person-years of follow-up, 574 incident strokes were documented, including 119 subarachnoid hemorrhages, 62 intraparenchymal hemorrhages, 303 ischemic strokes (264 thrombotic and 39 embolic infarctions), and 90 strokes of undetermined type. Among thrombotic infarctions, 90 large-artery occlusive infarctions and 142 lacunar infarctions were identified. Compared with women who ate fish less than once per month, those with higher intake of fish had a lower risk of total stroke: the multivariate relative risks (RRs), adjusted for age, smoking, and other cardiovascular risk factors, were 0.93 (95% confidence interval [CI], 0.65-1.34) for fish consumption 1 to 3 times per month, 0.78 (95% CI, 0.55-1.12) for once per week, 0.73 (95% CI, 0.47-1.14) for 2 to 4 times per week, and 0.48 (95% CI, 0.21-1.06) for 5 or more times per week (P for trend =.06). Among stroke subtypes, a significantly reduced risk of thrombotic infarction was found among women who ate fish 2 or more times per week (multivariate RR, 0.49; 95% CI, 0.26-0.93). Women in the highest quintile of intake of long-chain omega-3 polyunsaturated fatty acids had reduced risk of total stroke and thrombotic infarction, with multivariate RRs of 0.72 (95% CI, 0.53-0.99) and 0.67 (95% CI, 0.42-1.07), respectively. When stratified by aspirin use, fish and omega-3 polyunsaturated fatty acid intakes were inversely associated with risk of thrombotic infarction, primarily among women who did not regularly take aspirin. There was no association between fish or omega-3 polyunsaturated fatty acid intake and risk of hemorrhagic stroke.
Our data indicate that higher consumption of fish and omega-3 polyunsaturated fatty acids is associated with a reduced risk of thrombotic infarction, primarily among women who do not take aspirin regularly, but is not related to risk of hemorrhagic stroke.
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)
D van West, M Maes. Polyunsaturated fatty acids in depression.
SUMMARY Increasingly, there is a need in both research and clinical practice to document and quantify sleep and waking behaviors in a comprehensive manner. The Pittsburgh Sleep Diary (PghSD) is an instrument with separate components to be completed at bedtime and waketime. Bedtime components relate to the events of the day preceding the sleep, waketime components to the sleep period just completed. Two-week PghSD data is presented from 234 different subjects, comprising 96 healthy young middle-aged controls, 37 older men, 44 older women, 29 young adult controls and 28 sleep disorders patients in order to demonstrate the usefulness, validity and reliability of various measures from the instrument. Comparisons are made with polysomnographic and actigraphic sleep measures, as well as personality and circadian type questionnaires. The instrument was shown to have sensitivity in detecting differences due to weekends, age, gender, personality and circadian type, and validity in agreeing with actigraphic estimates of sleep timing and quality. Over a 12–31 month delay, PghSD measures of both sleep timing and sleep quality showed correlations between 0.56 and 0.81 (n= 39, P < 0.001).
The mechanisms of stress-related immune alterations have not been fully elucidated. Cell-mediated immune responses as well as antibody and certain cytokines are reported as being suppressed during times of high stress. However, the role of suppression vs dysregulation has not been established in human stress models. The effect of exam stress on regulatory cytokines in 16 healthy medical students was assessed by measuring type-1 (IFN-γ) and type-2 (IL-10) cytokines from 72-h PHA/PMA-stimulated PBMC 4 weeks before and 48 h after exams. Results demonstrated decreased IFN-γ accompanied by increased IL-10 during exam stress that resulted in a decreased IFN-γ:IL-10 ratio. There was a significant correlation between the cytokine response to PHA/PMA and number and subjective adjustment to daily hassles. Additionally, students who reported greater levels of loneliness also reported greater numbers of and poorer subjective adjustment to hassles. The differences were consistent in both males and females but did not correlate with AM cortisol levels. Additionally, when individuals were grouped into high vs low preexam hassle levels, the type-1/type-2 shift in the IFN-γ:IL-10 ratio occurred in the low hassles group only. These data suggest that psychologically stressful situations shift type-1/type-2 cytokine balance toward type-2 and result in an immune dysregulation rather than overall immunosuppression. This may partially explain the increased incidence of type-2-mediated conditions such as increased viral infections, latent viral expression, allergic/asthmatic reactions, and autoimmunity reported during periods of high stress.
A growing body of evidence indicates that patients with immune-inflammatory diseases experience an increased risk for cardiovascular morbidity and mortality. However, patients with immune-inflammatory diseases do not exhibit a corresponding increase in traditional coronary artery disease (CAD) risk factors that could explain the observed increase in CAD. Chronic inflammation is now accepted as playing a potentially important role in the promotion of atherosclerosis, a main cause of CAD. Evidence is also accumulating to suggest that the chronic systemic inflammation associated with immune-inflammatory diseases results in elevated levels of nontraditional CAD risk factors, such as biomarkers of inflammation, in patients with these conditions. Evaluation of only traditional CAD risk factors in these patients, therefore, may result in the underestimation of their future overall CAD risk. Using the Framingham patient cohort, we found associations between markers of inflammation and CAD risk overall. The contribution of inflammatory biomarkers should be considered along with the status of traditional CAD risk factors to gain a complete picture of the CAD risk in patients with underlying conditions that increase inflammation such as rheumatoid arthritis or systemic lupus erythematosus.
To address how interactions between polyunsaturated fatty acid (PUFA) levels and depressive symptoms were related to proinflammatory cytokine synthesis. Depression and stress promote proinflammatory cytokine production. Dietary intakes of omega-3 (n-3) and omega-6 (n-6) PUFAs also influence inflammation; high n-6:n-3 ratios enhance proinflammatory cytokine production, although n-3 has anti-inflammatory properties.
Blood samples from 43 older adults (mean age = 66.67 years, SD = 10.09) provided data on PUFAs and tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-6 soluble receptor (sIL-6r). Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale.
Depressive symptoms and n-6:n-3 ratios worked together to enhance proinflammatory cytokines beyond the contribution provided by either variable alone, with substantial variance explained by their interaction: 13% for IL-6 and 31% for TNF-alpha, whereas full models accounted for 18% and 40%, respectively. Although predicted cytokine levels were consistent across n-6:n-3 ratios with low depressive symptoms, higher n-6:n-3 ratios were associated with progressively elevated TNF-alpha and IL-6 levels as depressive symptoms increased. Higher levels of sIL-6r were associated with higher n-6:n-3 ratios. Six individuals who met the criteria for major depressive disorder had higher n-6:n-3 ratios and TNF-alpha, IL-6, and sIL-6r levels than those who did not meet the criteria; excluding these six individuals reduced the variance explained by the depressive symptoms and n-6:n-3 ratio interaction.
Diets with high n-6:n-3 PUFA ratios may enhance the risk for both depression and inflammatory diseases.
The n-6 and n-3 polyunsaturated fatty acids (PUFAs) are essential nutrients; intake of relatively small amounts of these fatty acids prevents nutritional deficiencies. Replacing dietary saturated fat with PUFAs may confer health gains. Experimental data support the notion that high intake of n-6 PUFAs may increase in vivo lipid peroxidation. This effect may be counteracted by dietary antioxidant supplementation. The influence of a high n-3 PUFA intake on measures of lipid peroxidation has been equivocal. In clinical trials, subjects who consumed diets rich in n-6 or n-3 PUFAs had fewer atherothrombotic endpoints than did control groups. In this report, data regarding the influence of PUFAs on lipid peroxidation as well as on cholesterol and glucose metabolism, hemostasis, and other aspects of interest are reviewed and discussed. Currently, daily intake of PUFAs as >10% of total energy is not recommended. Below this ceiling there is little evidence that high dietary intake of n-6 or n-3 PUFAs implies health risks.
Epidemiologic studies of fish consumption in relation to risk of stroke have yielded inconsistent results.
In this study, we examined the association between fish consumption and stroke incidence in women.
We analyzed data from a population-based prospective cohort of 34,670 women in the Swedish Mammography Cohort who were free of cardiovascular disease and cancer at baseline. Information on fish consumption was obtained by a self-administered questionnaire in 1997. Incident cases of stroke were ascertained from the Swedish Hospital Discharge Registry. We used Cox proportional hazards regression to estimate relative risks (RRs) and 95% CIs.
Over a mean follow-up of 10.4 y, we ascertained 1680 incident cases of stroke, including 1310 cerebral infarctions, 233 hemorrhagic strokes, and 137 unspecified strokes. Fish consumption was significantly inversely associated with risk of total stroke but not with cerebral infarction or hemorrhagic stroke. Compared with women in the lowest quintile of fish consumption (<1.0 serving of fish/wk), the multivariable RR of total stroke for women in the highest quintile (>3.0 servings of fish/wk) was 0.84 (95% CI: 0.71, 0.98; P for trend = 0.049). Consumption of lean fish but not of other fish types was inversely associated with risk of stroke. The multivariable RR of total stroke was 0.67 (95% CI: 0.49, 0.93; P for trend = 0.07) for ≥3 servings of lean fish/wk compared with that for no consumption.
These results suggest that the consumption of fish, especially of lean fish, may reduce risk of stroke in women. This trial was registered at clinicaltrials.gov as NCT01127698.
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.
Objective:
To support research and to provide food and nutrition practitioners with a strong foundation for nutrient-based counseling, there is a need for affordable automated 24-hour dietary recalls. Multiple days of intake, along with repeated reports over time, are needed to achieve stable indicators of individual intakes and to support evaluation of success in meeting dietary goals because of intraindividual intake variability. Little information has been published on subject responses, participation rates, and the perceived subject burden of repeated 24-hour recalls. Our aim was to determine the willingness of subjects to conduct eight 24-hour recalls via the Internet.
Design:
A study to validate a Web-based, automated, self-administered 24-hour recall (DietDay, Centrax Corporation, Chicago, IL).
Subjects/setting:
Two-hundred and sixty-one white and African-American subjects within 50 miles of the University of California-Los Angeles participated in the study. Subjects completed 3 DietDays at the study visits and another 5 days on their own. The last 2 DietDays were completed 1 and 2 months after the final clinic visit. Subjects were notified by automatic e-mail of the need for DietDay completion, and nonresponders were followed up with personalized e-mails and phone calls.
Results:
The perceived subject burden was minimal and, even after completing six recalls, 92% were willing to continue reporting their daily diets 1 and 2 months later. White subjects had a slightly higher rate of return, with 94% completing all eight recalls, compared to 91% of African-American subjects. Participants were able to access the Internet in their homes, offices, library, or homes of friends or family. It is also of interest that 82% of subjects believed the 24-hour recall was superior to a diet history in reflecting their normal diet.
Conclusion:
These results open up new opportunities for food and nutrition practitioners to strengthen their nutritional counseling in an efficient and affordable manner without additional time investment.
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.
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.
Anxiety disorders are a common group of psychiatric illnesses which have significant personal, family and societal costs. Current treatments have limited efficacy in many patients highlighting a need for new therapeutic approaches to be explored. Anxiety disorders exhibit marked comorbity with mood disorders suggesting the existence of mechanistic similarities. Such a notion is supported by observations that some conventional pharmacotherapies are both effective antidepressants and anxiolytics. As such, given that omega-3 PUFA supplementation may be effective in the treatment of major depressive disorder it is reasonable to propose that they may also possess anxiolytic properties. Experimental data in support of such a hypothesis is currently lacking although reduced abundance of omega-3 PUFA have been reported in patients with anxiety, while supplementation with omega-3 PUFA appears to inhibit activation of the HPA axis and can ameliorate some of the symptoms of anxiety. Clinical investigations carried out to date have, however, involved small numbers of participants. Larger trials using a variety of omega-3 PUFA species in clinically well-defined patients with anxiety will be required to demonstrate a therapeutic role for omega-3 PUFA in these disorders. Given the excellent side effect profile of omega-3 PUFA as well as their strong theoretical rationale, such future trials appear justified.
Despite the prevalence of sleep complaints among psychiatric patients, few questionnaires have been specifically designed to measure sleep quality in clinical populations. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. Clinical and clinimetric properties of the PSQI were assessed over an 18-month period with "good" sleepers (healthy subjects, n = 52) and "poor" sleepers (depressed patients, n = 54; sleep-disorder patients, n = 62). Acceptable measures of internal homogeneity, consistency (test-retest reliability), and validity were obtained. A global PSQI score greater than 5 yielded a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p less than 0.001) in distinguishing good and poor sleepers. The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.
To determine how well a seven-day interview-administered activity recall used in a large epidemioiogic study at Stanford University
reflected seven days of self-reported activity and directly measured physicai activity, 30 white males, mean age 52 years,
recorded daily physicai activity for a week, and half of these wore an ambuiatory solid-state minicomputer (Vitalog®) which measures continuous heart rate and motion. Total hours of moderate, hard, and hard plus very hard activity were not
significantly different for weekdays and weekends for self-report and recaii and were significantly correlated. Total energy
expenditure for subjects wearing the Vitalog averaged 38.5 ± 6.7 kcal/kg/day compared to en average of 37.7 ± 4.5 kcal/kg/day
for recaii or 39.6 ± 7.2 kcal/kg/day for self-report. Conditioning activities are best remembered followed by home or leisure
and job activities. Mean hours of sleep per week night were significantly greater reported by self-report than reported by
recall, but the two were significantly correlated. It is concluded that a seven-day activity recall accurately reflects mean
kcal/day expenditure, with conditioning activities being the best recalled. A self-report log used In conjunction with an
Interview- based seven-day recail might maximize accuracy of recall.
A Monthly Health Review was developed to monitor symptoms, illnesses and injuries among Air Traffic Controllers. Return rate of the mailed check-list exceeded 90 per cent. Diagnoses were generated from symptom clusters by computer algorithms. Telephone interview by physicians, laboratory analyses for serum pepsinogen I, and analyses of relations between symptom clusters and degree of disability all served to support the validity of the methodology. Such a system can provide inexpensive surveillance of morbidity in suitable populations.
The omega-3 polyunsaturated fatty acids derived from fish oils have been shown to modulate many factors believed to affect the pathogenesis of atherosclerosis. Because certain features of restenosis following angioplasty mimic some of the early changes of atherogenesis, some researchers have suggested that fish oil might prevent restenosis following angioplasty. We report the effects of omega-3 fatty acids on the rate of restenosis following percutaneous intraluminal coronary angioplasty (PTCA).
From August 1989 through September 1992, 551 patients were randomized to start receiving a daily dietary supplement of ten 1.0-g capsules containing 80.6% ethyl esters of omega-3 fatty acids providing 4.1 g eicosapentaenoic acid (EPA) and 2.8 g docosahexaenoic acid (DHA) for 6 months or an equal amount of an ethyl ester of corn oil. Four hundred seventy subjects who were well matched for risk factors completed successful angioplasty of one or multiple lesions in native coronary vessels and constituted the study cohort, of whom 447 were evaluable at 6 months after PTCA. The criteria for restenosis were that the quantitative coronary angiography at 6 months show a > 30% increase in narrowing at the stenosis site or loss of at least half of the gain achieved at the time of PTCA and final restenosis with < 50% luminal diameter remaining. In 93% of the patients, the end point was determined by angiography and in all except 1% of these by quantitative coronary angiography. Compliance with the fish oil supplement was good as judged by incorporation of EPA and DHA in plasma and red blood cell phospholipids. The restenosis rate among analyzable patients was 46% for corn oil and 52% for fish oil (P = .37). The addition of 200 mg alpha-tocopherol for all subjects during the study had no effect on restenosis rates.
This was the largest of such trials to date, and a supplement of 8 g/d of omega-3 fatty acids failed to prevent the usual high rate of restenosis after PTCA. No adverse effects were attributable to this large daily supplement of omega-3 fatty acids.
Respiratory infections are the leading cause of morbidity in community populations. We developed a structured interview based on the Health Review (Rose et al., Psychosom. Med. 40: 142-165, 1978) to provide a simple method for periodic assessment of infectious illness, particularly upper respiratory infections. Congruence between interview data and physician diagnoses demonstrated excellent agreement regarding the presence or absence of an infection. Subjects who showed a clinically significant increase in antibody titers to an influenza virus vaccine reported fewer than half as many respiratory infections in the subsequent year as subjects who did not show a significant response. Interrater and test-retest reliabilities were satisfactory. These data support the reliability and validity of this method of assessing infectious illnesses.
This paper considers an index to assess the success of blinding with application to a clinical trial of disulfiram. The index increases as the success of blinding increases, accounts for uncertain responses, and is scaled to an interval of 0.0 to 1.0, 0.0 being complete lack of blinding and 1.0 being complete blinding.
Conjugated linoleic acid (CLA) is a chemoprotective fatty acid that inhibits mammary, colon, forestomach, and skin carcinogenesis in experimental animals. We hypothesize that the ubiquitous chemoprotective actions of dietary CLA in extrahepatic tissues are dependent upon its role in modulating fatty acid composition and metabolism in liver, the major organ for lipid metabolism. This study begins to evaluate the role of CLA in lipid metabolism by determining the modulation of fatty acid composition by CLA. Female SENCAR mice were fed semipurified diets containing 0.0% (Diet A), 0.5% (Diet B), 1.0% (Diet C), or 1.5% (Diet D) CLA (by weight) for six weeks. Mice fed Diets B, C, and D exhibited lower body weights and elevated amounts of extractable total lipid in livers compared with mice fed diets without CLA (Diet A). Analyses of the fatty acid composition of liver by gas chromatography revealed that dietary CLA was incorporated into neutral and phospholipids at the expense of linoleate in Diets B, C, and D; oleate increased and arachidonate decreased in neutral lipids of CLA diet groups. In addition, increasing dietary CLA was associated with reduced linoleate in hepatic phospholipids. In an in vitro assay, CLA was desaturated to an unidentified 18:3 product to a similar extent as linoleate conversion to gamma-linolenate (9.88, and 13.63%, respectively). These data suggest that CLA may affect metabolic interconversion of fatty acids in liver that may ultimately result in modified fatty acid composition and arachidonate-derived eicosanoid production in extrahepatic tissues. In addition to determining how dietary CLA modulates eicosanoid synthesis, further work is needed to identify enzymatic products that may result from desaturation of CLA.
The Women's Health Initiative (WHI) is the largest research program ever initiated in the United States with a focus on diet and health. Therefore, it is important to understand and document the measurement characteristics of the key dietary assessment instrument: the WHI food frequency questionnaire (FFQ).
Data are from 113 women screened for participation in the WHI in 1995. We assessed bias and precision of the FFQ by comparing the intake of 30 nutrients estimated from the FFQ with means from four 24-hour dietary recalls and a 4-day food record.
For most nutrients, means estimated by the FFQ were within 10% of the records or recalls. Precision, defined as the correlation between the FFQ and the records and recalls, was similar to other FFQs. Energy adjusted correlation coefficients ranged from 0.2 (vitamin B12) to 0.7 (magnesium) with a mean of 0.5. The correlation for percentage energy from fat (a key measure in WHI) was 0.6. Vitamin supplement use was common. For example, almost half of total vitamin E intake was obtained from supplements. Including supplemental vitamins and minerals increased micronutrient correlation coefficients, which ranged from 0.2 (thiamin) to 0.8 (vitamin E) with a mean of 0.6.
The WHI FFQ produced nutrient estimate, that were similar to those obtained from short-term dietary recall and recording methods. Comparison of WHI FFQ nutrient intake measures to independent and unbiased measures, such as doubly labeled water estimates of energy expenditure, are needed to help address the validity of the FFQ in this population.
A single-slice computed tomography (CT) scan provides a criterion measure of total abdominal fat (TAF) and abdominal visceral fat (AVF), but this procedure is often prohibitive due to radiation exposure, cost, and accessibility. In the present study, the utility of anthropometric measures and estimates of trunk and abdominal fat mass by dual-energy X-ray absorptiometry (DXA) to predict CT measures of TAF and AVF (cross-sectional area, cm2) was assessed.
CT measures of abdominal fat (at the level of the L4-L5 inter-vertebral space), DXA scans, and anthropometric measures were obtained in 76 Caucasian adults ages 20-80 years.
Results demonstrated that abdominal sagittal diameter measured by anthropometry is an excellent predictor of sagittal diameter measured from a CT image (r=0.88 and 0.94; Total Error [TE]=4.1 and 3.1 cm, for men and women, respectively). In both men and women, waist circumference and abdominal sagittal diameter were the anthropometric measures most strongly associated with TAF (r=0.87 to 0.93; Standard Error of Estimate (SEE)=60.7 to 75.4 cm2) and AVF (r=0.84 to 0.93; SEE=0.7 to 30.0 cm2). The least predictive anthropometric measure of TAF or AVF was the commonly used waist-to-hip ratio (WHR). DXA estimates of trunk and abdominal fat mass were strongly associated with TAF (r=.94 to 0.97; SEE=36.9 to 50.9 cm2) and AVF (r=0.86 to 0.90; SEE=4.9 to 27.7 cm2).
The present results suggest that waist circumference and/or abdominal sagittal diameter are better predictors of TAF and AVF than the more commonly used WHR. DXA trunk fat and abdominal fat appear to be slightly better predictors of TAF but not AVF compared to these anthropometric measures. Thus DXA does not offer a significant advantage over anthropometry for estimation of AVF.
Background:
Psychologic stress in humans induces the production of proinflammatory cytokines, such as interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6), and that of the negative immunoregulatory cytokine, IL-10. An imbalance of omega6 to omega3 polyunsaturated fatty acids (PUFAs) in the peripheral blood causes an overproduction of proinflammatory cytokines. The omega3 PUFAs reduce the production of proinflammatory cytokines.
Methods:
This study examines whether an imbalance in omega6 to omega3 PUFAs in human blood predicts a greater production of proinflammatory cytokines in response to psychologic stress. Twenty-seven university students had serum sampled a few weeks before and after as well as 1 day before a difficult oral examination. We determined the omega6 and omega3 fractions in serum phospholipids as well as the ex vivo production of IFN-gamma, TNF-alpha, IL-6, IL-10, and IL-5 by diluted whole blood stimulated with polyclonal activators.
Results:
Academic examination stress significantly increased the ex vivo, stimulated production of IFN-gamma, TNF-alpha and IL-10, and the IFN-gamma/IL-5 production ratio. Subjects with lower serum omega3 PUFA levels or with a higher omega6/omega3 ratio had significantly greater stress-induced TNF-alpha and IFN-gamma responses than subjects with higher serum omega3 PUFAs and a lower omega6/omega3 ratio, respectively. Subjects with lower serum omega3 PUFA levels or with a higher omega6/omega3 ratio had a significantly higher stress-induced increase in the IFN-gamma/IL-5 ratio than the remaining subjects.
Conclusions:
Psychologic stress induces a Th-1-like or proinflammatory response in some subjects. An imbalance in the omega6 to omega3 PUFA ratio appears to predispose humans toward an exaggerated Th-1-like response and an increased production of monocytic cytokines, such as TNF-alpha, in response to psychologic stress. The results suggest that increased omega3 PUFA levels may attenuate the proinflammatory response to psychologic stress.
Several nutrients have been shown to influence immunologic and inflammatory responses in humans. Whether these effects translate into an improvement in clinical outcomes in critically ill patients remains unclear.
To examine the relationship between enteral nutrition supplemented with immune-enhancing nutrients and infectious complications and mortality rates in critically ill patients.
The databases of MEDLINE, EMBASE, Biosis, and CINAHL were searched for articles published from 1990 to 2000. Additional data sources included the Cochrane Controlled Trials Register from 1990 to 2000, personal files, abstract proceedings, and relevant reference lists of articles identified by database review.
A total of 326 titles, abstracts, and articles were reviewed. Primary studies were included if they were randomized trials of critically ill or surgical patients that evaluated the effect of enteral nutrition supplemented with some combination of arginine, glutamine, nucleotides, and omega-3 fatty acids on infectious complication and mortality rates compared with standard enteral nutrition, and included clinically important outcomes, such as mortality.
Methodological quality of individual studies was scored and necessary data were abstracted in duplicate and independently.
Twenty-two randomized trials with a total of 2419 patients compared the use of immunonutrition with standard enteral nutrition in surgical and critically ill patients. With respect to mortality, immunonutrition was associated with a pooled risk ratio (RR) of 1.10 (95% confidence interval [CI], 0.93-1.31). Immunonutrition was associated with lower infectious complications (RR, 0.66; 95% CI, 0.54-0.80). Since there was significant heterogeneity across studies, we examined several a priori subgroup analyses. We found that studies using commercial formulas with high arginine content were associated with a significant reduction in infectious complications and a trend toward a lower mortality rate compared with other immune-enhancing diets. Studies of surgical patients were associated with a significant reduction in infectious complication rates compared with studies of critically ill patients. In studies of critically ill patients, studies with a high-quality score were associated with increased mortality and a significant reduction in infectious complication rates compared with studies with a low-quality score.
Immunonutrition may decrease infectious complication rates but it is not associated with an overall mortality advantage. However, the treatment effect varies depending on the intervention, the patient population, and the methodological quality of the study.
Increasingly, there is a need in both research and clinical practice to document and quantify sleep and waking behaviors in a comprehensive manner. The Pittsburgh Sleep Diary (PghSD) is an instrument with separate components to be completed at bedtime and waketime. Bedtime components relate to the events of the day preceding the sleep, waketime components to the sleep period just completed. Two-week PghSD data is presented from 234 different subjects, comprising 96 healthy young middle-aged controls, 37 older men, 44 older women, 29 young adult controls and 28 sleep disorders patients in order to demonstrate the usefulness, validity and reliability of various measures from the instrument. Comparisons are made with polysomnographic and actigraphic sleep measures, as well as personality and circadian type questionnaires. The instrument was shown to have sensitivity in detecting differences due to weekends, age, gender, personality and circadian type, and validity in agreeing with actigraphic estimates of sleep timing and quality. Over a 12-31 month delay, PghSD measures of both sleep timing and sleep quality showed correlations between 0.56 and 0.81 (n = 39, P < 0.001).