A specific combined long-chain polyunsaturated fatty acid supplementation reverses fatty acid profile alterations in a mouse model of chronic asthma.
ABSTRACT: BACKGROUND:The immune-modulating potential of long-chain polyunsaturated fatty acids (LCPUFAs) based on their conversion into lipid mediators in inflammatory situations has been proven by several studies. Respecting the immune-modulative role of lipid mediators in bronchoconstriction, airway inflammation and resolution of inflammatory processes, LCPUFAs play an important role in asthma. To design a disease-specific and most beneficial LCPUFA supplementation strategy, it is essential to understand how asthma alters LCPUFA profiles. Therefore, this study characterizes the alterations of LCPUFA profiles induced by allergic asthma. In addition, this study explores whether a simple eicosapentaenoic acid (EPA) alone or a specific combined LCPUFA supplementation could restore imbalanced LCPUFA profiles. METHODS:Mice were sensitized with a daily dose of 40??g house dust mite (HDM)-extract in a recall model and fed with either normal diet, EPA or a specific combined (sc)-LCPUFA supplementation containing EPA, docosahexaenoic acid (DHA), ? -linolenic acid (GLA) and stearidonic acid (SDA) for 24?days. After recall with HDM, mice were sacrificed and blood and lung tissue were collected. Fatty acid profiles were determined in plasma, blood cells and lung cells of asthmatic mice by capillary gas-chromatography. RESULTS:In lung cells of asthmatic mice, arachidonic acid (AA, p?
Project description:Lipid mediators derived from omega (n)-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFA) play key roles in bronchoconstriction, airway inflammation, and resolution processes in asthma. This study compared the effects of dietary supplementation with either a combination of LCPUFAs or eicosapentaenoic acid (EPA) alone to investigate whether the combination has superior beneficial effects on the outcome of asthmatic mice. Mice were sensitized with house dust mite (HDM) extract, and subsequently supplemented with either a combination of LCPUFAs or EPA alone in a recall asthma model. After the final HDM and LCPUFA administration, airway hyperresponsiveness (AHR), bronchoalveolar lavages, and lung histochemistry were examined. Lipid mediator profiles were determined by liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). The LCPUFA combination reduced AHR, eosinophilic inflammation, and inflammatory cytokines (IL-5, IFN-?, and IL-6) in asthmatic mice, whereas EPA enhanced inflammation. The combination of LCPUFAs was more potent in downregulating EPA-derived LTB<sub>5</sub> and LTC<sub>5</sub> and in supporting DHA-derived RvD1 and RvD4 (2.22-fold and 2.58-fold higher levels) than EPA alone. Ex vivo experiments showed that LTB<sub>5</sub> contributes to granulocytes' migration and M1-polarization in monocytes. Consequently, the LCPUFA combination ameliorated airway inflammation by inhibiting adverse effects of EPA and promoting pro-resolving effects supporting the lipid mediator-dependent resolution program.
Project description:Despite numerous studies investigating n-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation and inflammatory bowel diseases (IBD), the extent to which dietary n-3 LCPUFAs incorporate in gastrointestinal (GI) tissues and correlate with red blood cell (RBC) n-3 LCPUFA content is unknown. In this study, mice were fed three diets with increasing percent of energy (%en) derived from eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA). Dietary levels reflected recommended intakes of fish/fish oil by the American Heart Association. We analyzed the FA composition of phospholipids extracted from RBCs, plasma, and GI tissues. We observed that the 0.1%en EPA+DHA diet was sufficient to significantly increase the omega-3 index (RBC EPA+DHA) after 5 week feeding. The baseline EPA levels were 0.2-0.6% across all tissues increasing to 1.6-4.3% in the highest EPA+DHA diet; these changes resulted in absolute increases of 1.4-3.9% EPA across tissues. The baseline DHA levels were 2.2-5.9% across all tissues increasing to 5.8-10.5% in the highest EPA+DHA diet; these changes resulted in absolute increases of 3.2-5.7% DHA across tissues. These increases in EPA and DHA across all tissues resulted in strong (r>0.91) and significant (P<0.001) linear correlations between the omega-3 index and plasma/GI tissue EPA+DHA content, suggesting that the omega-3 index reflects the relative amounts of EPA+DHA in GI tissues. These data demonstrate that the GI tissues are highly responsive to dietary LCPUFA supplementation and that the omega-3 index can serve as a valid biomarker for assessing dietary EPA+DHA incorporation into GI tissues.
Project description:Allergy has sharply increased in affluent Western countries in the last 30 years. N-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) may protect the immune system against development of allergy.We prospectively categorized illnesses by body system in a subset of 91 children from the Kansas City cohort of the DIAMOND (DHA Intake and Measurement of Neural Development) study who had yearly medical records through 4 years of age. As infants, they were fed either a control formula without LCPUFA (n = 19) or one of three formulas with LCPUFA from docosahexaenoic acid (DHA) and arachidonic acid (ARA) (n = 72).Allergic illnesses in the first year were lower in the combined LCPUFA group compared to the control. LCPUFAs significantly delayed time to first allergic illness (p = 0.04) and skin allergic illness (p = 0.03) and resulted in a trend to reduced wheeze/asthma (p = 0.1). If the mother had no allergies, LCPUFAs reduced the risk of any allergic diseases (HR = 0.24, 95% CI = 0.1, 0.56, p = 0.0.001) and skin allergic diseases (HR = 0.35, 95% CI = 0.13, 0.93, p = 0.04). In contrast, if the mother had allergies, LCPUFAs reduced wheezing/asthma (HR = 0.26, 95% CI = 0.07, 0.9, p = 0.02).LCPUFA supplementation during infancy reduced the risk of skin and respiratory allergic diseases in childhood with effects influenced by maternal allergies.
Project description:Next generation sequencing (NGS) results demonstrate the modulative capacity of LCPUFAs on dysregulated miRNA expression in asthma. Methods: Sequencing of miRNA was performed by NGS from lung tissue of asthmatic and control mice with normal diet, as well as of LCPUFA supplemented asthmatic mice using Illumina miSeq. Conclusion: Our results demonstrate the modulative capacity of LCPUFAs on dysregulated miRNA expression in asthma. Overall design: Lungs of LCPUFA-treated asthmatic C57BL/6 mice and respective controls were analyzed with n=4-5 via NGS
Project description:BACKGROUND:Elevated resting heart rate (HR) has emerged as a new risk factor for all-cause and cardiovascular mortality. The effect of marine-derived omega-3 long-chain polyunsaturated fatty acid (n-3 LCPUFAs) supplementation on HR was investigated as an outcome in many clinical trials. The present study was to provide an updated meta-analysis on the HR-slowing effect of n-3 LCPUFAs, and to differentiate the chronotropic effect between eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). METHODS:PubMed and Cochrane databases were searched for relevant articles examining the effects of n-3 PUFAs on HR through May 2017. A random-effects model was used to generate the pooled effect sizes and 95% confidence intervals (CIs). The pooled effect sizes were presented as weighted mean differences (WMDs). RESULTS:A total of 51 randomized controlled trials (RCTs) with approximately 3000 participants were included in this meta-analysis. Compared to placebo, n-3 PUFA supplementation mildly but significantly reduced HR (-2.23 bpm; 95% CI: -3.07, -1.40 bpm). Moderate evidence of heterogeneity was observed among included trials (I 2?=?49.1%, P heterogeneity?<?0.001). When DHA and EPA were separately administered, modest HR reduction was observed in trials that supplemented with DHA (-2.47 bpm; 95% CI: -3.47, -1.46 bpm), but not in trials with EPA. CONCLUSIONS:The present meta-analysis provides strong clinical evidence demonstrating the effect of heart rate reduction by n-3 LCPUFA supplementation. When DHA or EPA administered alone, heart rate was slowed by DHA rather than by EPA.
Project description:Long-chain polyunsaturated fatty acids (LCPUFA) are important for brain development and function, maybe especially during adolescence. Observational studies have demonstrated an association between fish consumption (a source of LCPUFA) and cognition in adolescents, but intervention trials are lacking. The goal of the current study was to investigate the effect of one year of krill oil (a source of LCPUFA) supplementation on the cognitive performance of adolescents with a low Omega-3 Index (O3I ? 5%). A double-blind, randomized, and placebo-controlled supplementation trial with repeated measurements (baseline (T0), three months (T1), six months (T2), and 12 months (T3)) in adolescents (267 randomized) was executed. Participants were randomized to 400 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day in Cohort I or placebo and 800 mg EPA + DHA per day in Cohort II or placebo. O3I was monitored by a finger prick at all time points. At T0, T2, and T3, participants executed a neurocognitive test battery. Covariate corrected mixed models were run with either condition (krill or placebo) or O3I as predictors. Krill oil supplementation led to a small but significant increase in mean O3I, but few participants increased to the intended O3I range (8-11%). There was no significant effect of supplementation on the neurocognitive tests, nor a relationship between O3I and neurocognitive test scores. The increase in O3I was small in most participants, probably due to non-compliance. Possibly the increase in O3I was too small to demonstrate an effect. More research on the influence of LCPUFAs on cognition in adolescents is needed.
Project description:<h4>Background</h4>Previous studies suggested that dietary fatty acids could affect blood lipids by interacting with genetic variations in fatty acid desaturase 1 (FADS1). However, little is known about their direct effects on coronary artery disease (CAD). The aim of this study was to evaluate whether dietary n-3 long-chain polyunsaturated fatty acids (LCPUFAs)-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) could modulate the effect of FADS1 rs174547 polymorphism on CAD.<h4>Methods</h4>FADS1 single-nucleotide polymorphisms rs174547 genotypes were measured in 440 CAD patients and 838 healthy controls. Dietary EPA and DHA intakes were assessed with a validated quantitative frequency food questionnaire. The association between FADS1 rs174547 and CAD was estimated using logistic regression under both dominant and additive genetic models. The interactions between rs174547 polymorphism and LCPUFAs were analyzed by using multiple logistic regression and the "genotype × n-3 LCPUFAs" interaction term was included into the model.<h4>Results</h4>We found that the minor T allele of FADS1 rs174547 increased CAD risk (OR = 1.36, 95%CIs 1.03-1.80), and observed significant interaction between rs174547 and dietary EPA intakes on CAD (P-interaction = 0.028). The T-allele was only associated with higher CAD risk among individuals with lower dietary EPA intakes, but not in those with higher EPA intakes. Similarly, significant interaction was also observed between rs174547 and dietary DHA intakes on CAD (P-interaction = 0.020).<h4>Conclusions</h4>Dietary n-3 LCPUFA intakes could modulate the association between FADS1 rs174547 polymorphism and CAD. High dietary n-3 LCPUFA intakes could negate the unfavorable effect of genetic variation in FADS1 on CAD in middle-aged and elderly Chinese population.
Project description:This scoping review examines the evidence for n-3 long-chain polyunsaturated fatty acid [LCPUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] supplementation in clinical cancer therapy. A comprehensive literature search was performed to identify relevant clinical intervention studies conducted through August 2020. Fifty-seven unique cancer trials, assessing EPA and/or DHA supplementation pre- or post-treatment, concomitant with neoadjuvant chemotherapy, radiation or surgery, or in palliative therapy were included. Breast, head and neck, gastrointestinal, gastric, colorectal/rectal, esophageal, leukemia/lymphoma, lung, multiple myeloma and pancreatic cancers were investigated. Across the spectrum of cancers, the evidence suggests that supplementation increased or maintained body weight, increased progression-free and overall survival, improved overall quality of life, resulted in beneficial change in immune parameters and decreased serious adverse events. Taken together, the data support that EPA and/or DHA could be used to improve outcomes important to the patient and disease process. However, before incorporation into treatment can occur, there is a need for randomized clinical trials to determine the dose and type of n-3 LCPUFA intervention required, and expansion of outcomes assessed and improved reporting of outcomes.
Project description:After birth, preterm infants are deficient in arachidonic acid (ARA), docosahexaenoic acid (DHA), and antioxidants, increasing their risk of oxidative stress-related pathologies. The principal aim was to evaluate if supplementation with long-chain polyunsaturated fatty acids (LCPUFAs) improves antioxidant defenses. In total, 21 preterm infants were supplemented with ARA and DHA in a 2:1 ratio (ARA:DHA-S) or with medium-chain triglycerides (MCT-S). Plasma n-3 and n-6 LCPUFAs were measured at birth, postnatal day 28, and 36 weeks of postmenstrual age (36 WPA) by gas chromatography-mass spectroscopy. Plasma antioxidants (glutathione (GSH), catalase, and thiols) and oxidative damage biomarkers (malondialdehyde (MDA), carbonyls) were analyzed at the same time points by spectrophotometry, and scores of antioxidant status (Antiox-S) and oxidative damage (Proxy-S) were calculated. At 36 WPA, linoleic acid (LA) and dihomo--linolenic acid (DGLA) were decreased in ARA:DHA-S compared to the MCT-S group (LA: ARA:DHA-S = 18.54 1.68, MCT-S = 22.80 1.41; p = 0.018; DGLA: ARA:DHA-S = 1.68 0.38, MCT-S = 2.32 0.58; p = 0.018). Furthermore, α-linolenic acid (ALA) was increased in ARA:DHA-S (ARA:DHA-S = 0.52 0.33, MCT-S = 0.22 0.10; p = 0.018). Additionally, LA:DHA ratio was decreased in the ARA:DHA-S compared to control group (ARA:DHA-S = 6.26 2.35, MCT-S = 8.21 2.65; p = 0.045). By the end of supplementation (36 WPA), catalase, thiol groups, and Antiox-S were significantly higher in neonates receiving ARA:DHA-S compared to those receiving MCT-S, with no differences in oxidative stress biomarkers. In conclusion, ARA:DHA supplementation in preterm neonates resulted in an overall improvement in antioxidant to oxidant balance and a decrease in early fatty acid precursors of the n-6 relative to the n-3 pathway. These effects may reduce oxidative stress and inflammation.
Project description:Life expectancy is increasing and so is the prevalence of age-related non-communicable diseases (NCDs). Consequently, older people and patients present with multi-morbidities and more complex needs, putting significant pressure on healthcare systems. Effective nutrition interventions could be an important tool to address patient needs, improve clinical outcomes and reduce healthcare costs. Inflammation plays a central role in NCDs, so targeting it is relevant to disease prevention and treatment. The long-chain omega-3 polyunsaturated fatty acids (omega-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are known to reduce inflammation and promote its resolution, suggesting a beneficial role in various therapeutic areas. An expert group reviewed the data on omega-3 LCPUFAs in specific patient populations and medical conditions. Evidence for benefits in cognitive health, age- and disease-related decline in muscle mass, cancer treatment, surgical patients and critical illness was identified. Use of DHA and EPA in some conditions is already included in some relevant guidelines. However, it is important to note that data on the effects of omega-3 LCPUFAs are still inconsistent in many areas (e.g., cognitive decline) due to a range of factors that vary amongst the trials performed to date; these factors include dose, timing and duration; baseline omega-3 LCPUFA status; and intake of other nutrients. Well-designed intervention studies are required to optimize the effects of DHA and EPA in specific patient populations and to develop more personalized strategies for their use.