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Causal Effects of Serum Levels of n-3 or n-6 Polyunsaturated Fatty Acids on Coronary Artery Disease: Mendelian Randomization Study.
Park, S, Lee, S, Kim, Y, Lee, Y, Kang, M, Kim, K, Kim, Y, Han, S, Lee, H, Lee, J, et al
Nutrients. 2021;(5)
Abstract
We aimed to investigate the causal effects of n-3 and n-6 polyunsaturated fatty acids (PUFAs) on the risk of coronary artery disease (CAD) through Mendelian randomization (MR) analysis. This MR study utilized a genetic instrument developed from previous genome-wide association studies for various serum n-3 and n-6 PUFA levels. First, we calculated the allele scores for genetic predisposition of PUFAs in individuals of European ancestry in the UK Biobank data (N = 337,129). The allele score-based MR was obtained by regressing the allele scores to CAD risks. Second, summary-level MR was performed with the CARDIoGRAMplusC4D data for CAD (N = 184,305). Higher genetically predicted eicosapentaenoic acid and dihomo-gamma-linolenic acid levels were significantly associated with a lower risk of CAD both in the allele-score-based and summary-level MR analyses. Higher allele scores for linoleic acid level were significantly associated with lower CAD risks, and in the summary-level MR, the causal estimates by the pleiotropy-robust MR methods also indicated that higher linoleic acid levels cause a lower risk of CAD. Arachidonic acid showed significant causal estimates for a higher risk of CAD. This study supports the causal effects of certain n-3 and n-6 PUFA types on the risk of CAD.
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Impact of Omega-3 Fatty Acids Among Other Nonpharmacological Interventions on Behavior and Quality of Life in Children with Compromised Conduct in Spain.
Rodríguez-Hernández, PJ, Canals-Baeza, A, Santamaria-Orleans, A, Cachadiña-Domenech, F
Journal of dietary supplements. 2020;(1):1-12
Abstract
The aim of this study was to assess the impact of omega-3 fatty acid supplementation among other nonpharmacological treatments on mental health and quality of life (QOL) of children with behavioral disorders. An observational multicenter study of 6- to 12-year-old children with behavior-related problems was performed in Spain with a three-month follow-up assessment. The Kidscreen-10 and Strengths and Difficulties Questionnaires (SDQ) were used to assess effectiveness of each intervention. Characteristics of study population were compared with those of the general population. Subanalyses of two homogenous subgroups, who received versus did not receive dietary supplementation with omega-3 fatty acids, were performed. The study included 942 children (69.1% male) with a mean (SD) age of 8.5 (1.8) years. Overall, patients' health status and QOL significantly improved at three months (p < .001). Scores on the SDQ also improved, with significant reductions on all subscales (p < .05). Comparison of SDQ results with the same-age general population showed higher overall scores in the study population (8.5 [5.5] vs. 18.6 [8.1], respectively) and on all the subscales (p < .001 in all cases). The omega-3 fatty acid supplementation subgroup presented greater improvements in each category of SDQ (p < .05), except for the emotion subscale. Omega-3 fatty acid supplementation alone or in combination with other nonpharmacological treatments is effective in improving children's mental health. Overall, nonpharmacological recommendations currently made by pediatricians seem to be effective in improving the perceived health status and patients' QOL and in the reduction of health problems, especially hyperactivity/inattention and conduct problems.
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Prenatal oxidative balance and risk of asthma and allergic disease in adolescence.
Sordillo, JE, Rifas-Shiman, SL, Switkowski, K, Coull, B, Gibson, H, Rice, M, Platts-Mills, TAE, Kloog, I, Litonjua, AA, Gold, DR, et al
The Journal of allergy and clinical immunology. 2019;(6):1534-1541.e5
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Abstract
BACKGROUND Fetal oxidative balance (achieved when protective prenatal factors counteract sources of oxidative stress) might be critical for preventing asthma and allergic disease. OBJECTIVE We examined prenatal intakes of hypothesized protective nutrients (including antioxidants) in conjunction with potential sources of oxidative stress in models of adolescent asthma and allergic disease. METHODS We used data from 996 mother-child pairs in Project Viva. Exposures of interest were maternal prepregnancy body mass index and prenatal nutrients (energy-adjusted intakes of vitamins D, C, and E; β-carotene; folate; choline; and n-3 and n-6 polyunsaturated fatty acids [PUFAs]), air pollutant exposures (residence-specific third-trimester black carbon or particulate matter with a diameter of less than 2.5 μm [PM2.5]), acetaminophen, and smoking. Outcomes were offspring's current asthma, allergic rhinitis, and allergen sensitization at a median age of 12.9 years. We performed logistic regression. Continuous exposures were log-transformed and modeled as z scores. RESULTS We observed protective associations for vitamin D (odds ratio [OR], 0.69 [95% CI, 0.53-0.89] for allergic rhinitis), the sum of the n-3 PUFAs eicosapentaenoic acid and docosahexaenoic acid (OR, 0.81 [95% CI, 0.66-0.99] for current asthma), and the n-3 PUFA α-linolenic acid (OR, 0.78 [95% CI, 0.64-0.95] for allergen sensitization and OR, 0.80 [95% CI 0.65-0.99] for current asthma). Black carbon and PM2.5 were associated with an approximately 30% increased risk for allergen sensitization. No multiplicative interactions were observed for protective nutrient intakes with sources of oxidative stress. CONCLUSIONS We identified potential protective prenatal nutrients (vitamin D and n-3 PUFAs), as well as adverse prenatal pro-oxidant exposures that might alter the risk of asthma and allergic disease into adolescence.
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Red Blood Cell Fatty Acids and Incident Diabetes Mellitus in the Women's Health Initiative Memory Study.
Harris, WS, Luo, J, Pottala, JV, Margolis, KL, Espeland, MA, Robinson, JG
PloS one. 2016;(2):e0147894
Abstract
CONTEXT The relations between dietary and/or circulating levels of fatty acids and the development of type 2 diabetes is unclear. Protective associations with the marine omega-3 fatty acids and linoleic acid, and with a marker of fatty acid desaturase activity delta-5 desaturase (D5D ratio) have been reported, as have adverse relations with saturated fatty acids and D6D ratio. OBJECTIVE To determine the associations between red blood cell (RBC) fatty acid distributions and incident type 2 diabetes. DESIGN Prospective observational cohort study nested in the Women's Health Initiative Memory Study. SETTING General population. SUBJECTS Postmenopausal women. MAIN OUTCOME MEASURES Self-reported incident type 2 diabetes. RESULTS There were 703 new cases of type 2 diabetes over 11 years of follow up among 6379 postmenopausal women. In the fully adjusted models, baseline RBC D5D ratio was inversely associated with incident type 2 diabetes [Hazard Ratio (HR) 0.88, 95% confidence interval (CI) 0.81-0.95) per 1 SD increase. Similarly, baseline RBC D6D ratio and palmitic acid were directly associated with incident type 2 diabetes (HR 1.14, 95% CI 1.04-1.25; and HR 1.24, 95% CI 1.14-1.35, respectively). None of these relations were materially altered by excluding incident cases in the first two years of follow-up. There were no significant relations with eicosapentaenoic, docosahexaenoic or linoleic acids. CONCLUSIONS Whether altered fatty acid desaturase activities or palmitic acid levels are causally related to the development of type 2 diabetes cannot be determined from this study, but our findings suggest that proportions of certain fatty acids in RBC membranes are associated with risk for type 2 diabetes.
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The ZONE Diet and Metabolic Control in Type 2 Diabetes.
Stulnig, TM
Journal of the American College of Nutrition. 2015;:39-41
Abstract
Obesity is associated with chronic inflammation of the adipose tissue, which contributes to obesity-associated complications such as insulin resistance and type 2 diabetes. The increased inflammatory response seems to be directly related to modern nutrition, particularly aspects of fat quality and macronutrient composition. We have recently published an observational study investigating the practicability and effects of a combined dietary intervention with increased relative protein content and low-glycemic-index carbohydrates, supplemented with omega-3 polyunsaturated fatty acids (PUFAs), on metabolic control and inflammatory parameters in real-life situations in patients with type 2 diabetes. The primary efficacy parameter was the change in HbA1c, and secondary parameters included change in systemic inflammation (measured by ultrasensitive C-reactive protein), body weight, waist circumference, fat mass, and homeostasis model assessment-insulin resistance. Counseling a protein-enriched and low-glycemic-index diet supplemented with long-chain omega-3 PUFAs in a real-life clinical setting improved glycemic control, waist circumference, and silent inflammation in overweight or obese patients with type 2 diabetes.
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Relationship between Fatty Acid Habitual Intake and Early Inflammation Biomarkers in Individuals with and without Type 2 Diabetes in Mexico.
Guadarrama-López, AL, Valdés-Ramos, R, Kaufer-Horwitz, M, Harbige, LS, Contreras, I, Martínez-Carrillo, BE
Endocrine, metabolic & immune disorders drug targets. 2015;(3):234-41
Abstract
BACKGROUND Lifestyle changes have led to a high global incidence of type 2 Diabetes mellitus (T2DM). Evidence suggests beneficial effects of the intake of n-3 and n-6 polyunsaturated fatty acids (PUFA) in patients with T2DM. OBJECTIVE To investigate the relationship between habitual fatty acid intake and inflammatory biomarkers in Mexican individuals with and without T2DM. METHODS A cross-sectional study of 120 adults with and 120 without T2DM; anthropometric assessments (BMI, waist circumference and body fat), blood pressure, PUFA intake, biochemical analyses (glucose and lipid profile) and inflammation biomarkers (IFN-γ, TNF-α, IL-1 β, IL-2, IL-6, IL-8 and IL-13) was undertaken. RESULTS Low n-3 intake was found in both groups (0.68 ± 0.55g/day in T2DM vs 0.81 ± 0.53 g/day in non-T2DM). Comparison between groups showed significantly higher concentrations of triacylglcerols (p=.001) and IL-6 (p=.018) in the T2DM group, as well as significant correlations between serum TNF-α and total n-3 fatty acid intake (r=.507, p= .001), EPA (r=.284, p=.002), DHA (r=.404, p=.001), and a weak but significant correlation between serum IL-1β and total PUFA (r=.245, p=.005), total n-3 (r=.214, p=.019) and total n-6 (r=.241, p=.008) intake. CONCLUSIONS Patients with T2DM had a tendency for higher pro-inflammatory cytokines than subjects without T2DM. There was an association between PUFA intake and pro-inflammatory biomarkers in patients with T2DM. Further studies of anti-inflammatory nutrients and plasma and cell fatty acid profiles are needed to corroborate the present findings in patients with and without T2DM.
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Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment.
Saunders, EF, Reider, A, Singh, G, Gelenberg, AJ, Rapoport, SI
Bipolar disorders. 2015;(7):729-42
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Abstract
OBJECTIVES Omega (n)-3 and n-6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n-3 PUFAs would be lower and those of n-6 PUFAs higher in subjects with bipolar disorder (BD) compared to healthy controls (HCs), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n-3 but lower n-6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids. METHODS This observational, parallel group study compared biomarkers between HCs (n = 31) and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow-up). Plasma concentrations of five PUFAs [linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], two saturated fatty acids (palmitic acid and stearic acid) and two monounsaturated fatty acids (palmitoleic acid and oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFAs, ratios of n-3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio of n-6:n-3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t-tests, and between the BD group at baseline and follow-up using paired t-tests. Comparison of categorical variables was performed using chi-square tests. Pearson's r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis. RESULTS UE EPA was lower in subjects with BD than in HCs, with a large effect size (Cohen's d = 0.86, p < 0.002); however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between the BD and HC groups after Bonferroni correction for 40 comparisons, at p < 0.001. Neither depressive severity nor mania severity was correlated significantly with any PUFA concentration. Exploratory comparison showed lower UE:E EPA in the BD than the HC group (p < 0.0001). At follow-up in the BD group, UE, E DHAALA, and UE EPAALA were decreased (p < 0.002). Exploratory correlations of clinical variables revealed that mania severity and suicidality were positively correlated with UE:E EPA ratio, and that several plasma levels and ratios correlated with panic disorder and psychosis. Depressive severity was not correlated with any ratio. No plasma fatty acid level or ratio correlated with self-reported n-3 PUFA intake or use of medication by class. CONCLUSIONS A large effect size of reduced UE EPA, and a lower plasma UE:E concentration ratio of EPA in the symptomatic BD state may be important factors in vulnerability to a mood state. Altered n-3 PUFA ratios could indicate changes in PUFA metabolism concurrent with symptom improvement. Our findings are consistent with preclinical and postmortem data and suggest testing interventions that increase n-3 and decrease n-6 dietary PUFA intake.
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Erythrocyte membrane polyunsaturated fatty acid (pufa) levels in a sample of patients with schizophrenia and relation with clinical and progression variables.
Montesinos-Rueda, L, Cañete-Crespillo, J, Palma-Sevillano, C, Giné-Serven, E
Actas espanolas de psiquiatria. 2015;(5):170-6
Abstract
INTRODUCTION Previous studies have shown that erythrocyte cell membranes in patients with schizophrenia contain considerably less omega-3 fatty acids, particularly EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), reflecting the lower levels present in neuronal and central nervous system membranes. This phenomenon, linked to genetic, metabolic, or dietary factors, has been associated with the development of schizophrenia and the risk of developing and the severity of metabolic syndrome. METHODS This study is an observational study conducted in a sample of 31 patients with schizophrenia treated at the Mataró Mental Health Center (Barcelona). Its aim was to relate the erythrocyte levels of omega 3 with the clinical severity of schizophrenia and dietary habits. EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid) and other membrane lipid levels were determined, as well as psychopathology, cognitive, and social functioning measures, previous evolution, and finally a survey of dietary habits. RESULTS Our results did not show a statistically significant correlation between erythrocyte omega-3 levels and psychopathological and clinical severity variables. Higher, statistically significant, levels were found in the group of women and in subjects with more days of admission to the day hospital. In contrast, lower values were obtained in subjects treated with long-acting antipsychotics and in sunflower oil consumers. CONCLUSIONS Despite not being able to demonstrate our working hypothesis, significant correlations were found that were consistent with published findings in the current literature. The need for studies with larger samples and groups of healthy controls is postulated.
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Omega-3 Fatty acids and gestational length in a high-risk psychiatric population due to psychiatric morbidity and medication exposure during pregnancy.
Freeman, MP, Cohen, LS, McInerney, K
Journal of clinical psychopharmacology. 2014;(5):627-32
Abstract
OBJECTIVE Premature birth is associated with infant morbidity and mortality. Women with psychiatric disorders represent an at-risk population for premature delivery and other obstetrical complications. The primary aim of this study was to assess the association between omega-3 fatty acid use and length of gestation. METHODS Data from the National Pregnancy Registry for Atypical Antipsychotics were used. This prospective study included pregnant women exposed and unexposed to atypical antipsychotics during pregnancy. The outcomes of gestational length, birth weight, and preeclampsia were examined in relation to omega-3 use during pregnancy. Omega-3 use was operationalized from a first-trimester interview as a dichotomous variable. RESULTS Of 361 women who were examined for eligibility, 233 women had a singleton birth as well as a valid response on the omega-3 item and information on at least one of the outcome measures. Ninety-seven (41.6%) women used omega-3 during pregnancy. Omega-3 users were older, more educated, and more likely to be married than nonusers. The users were less likely to have smoked during their first trimester and were marginally less likely to use antidepressant medications anytime during pregnancy. There were no significant differences in primary diagnoses or atypical antipsychotic, alcohol, or prenatal vitamin use. In an unadjusted model, there was a significant increase of between 4 and 5 days (0.65 weeks; 0.00-1.25) in gestational length among the omega-3 users. This result was no longer significant after adjusting for confounding variables, with an increase of approximately 4 days (0.53 weeks; -0.11 to 1.16). Omega-3 use was not significantly associated with a difference in birth weight or preeclampsia. CONCLUSIONS We found a trend for a modestly increased length of gestation among the omega-3 fatty acid users, although these were not significant after controlling for the exposures of smoking and antidepressant use. We did not find a decreased risk for preeclampsia among the users of omega-3 fatty acids or increased birth weight. In consideration of the risk factors for obstetrical and neonatal complications as well as implications for infant and child development, it would be clinically important to understand the variables that may additively decrease obstetrical risks in this population.
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Effect of PUFA on patients with hypertension: a hospital based study.
Shantakumari, N, Eldeeb, RA, Ibrahim, SA, Sreedharan, J, Otoum, S
Indian heart journal. 2014;(4):408-14
Abstract
INTRODUCTION Hypertension affects more than a quarter of the global adult population. Studies conducted worldwide suggest an overall small, yet useful, role of omega-3 PUFAs in reducing blood pressure in hypertensive patients. However there is no substantial data in this regard from population based in Middle East and Asia. OBJECTIVES To determine the effects of (omega-3) PUFA supplementation on the blood pressure of hypertensive patient. To identify if male and female hypertensive patients respond differently to PUFA. To identify if response of hypertensive patients to PUFA varies with the duration of hypertension and co-existence of diabetes/dyslipidemia. MATERIALS AND METHODS This observational study was conducted among hypertensive patients visiting OPD of the Gulf Medical College Hospital, Ajman, UAE, during the period Jan-Dec 2012. A total of 100 hypertensive patients on treatment with their antihypertensive medications, 50 of whom were taking n-3 PUFA supplementation, were followed up for a period of 3 months. Comparisons were drawn between the BP recordings at the time of enrollment in the study and their follow up values 3 months after enrollment. RESULTS There was a statistically significant reduction in both the systolic and diastolic blood pressures after 3 months of PUFA therapy. The BP lowering effect of PUFA was more in males. A statistically significant reduction in BP was noted in non-diabetic patients and patients with long standing hypertension. CONCLUSION Findings of the study suggest that omega-3 PUFA dietary supplements augment the benefits of pharmacotherapy in hypertension.