Polyunsaturated Fatty Acid Supplementation Research Articles

Assessing the Highest Level of Evidence from Randomized Controlled Trials in Omega-3 Research.

Over the years, there has been heightened interest in the health benefits of n-3 polyunsaturated fatty acids (PUFA) in reducing chronic diseases such as, cardiovascular disease (CVD), cancer, type 2 diabetes, and acute macular degeneration (AMD). Due to inconsistent findings in the evidence, a review to critically examine the plethora of evidence from randomized controlled trials (RCTs) in n-3 PUFA research was undertaken. The aim of this review is to study the highest level of evidence and to identify gaps in n-3 PUFA research. RCTs were originally designed for pharmaceutical research and later adopted for nutrition and food-related research. RCTs with active diseases assume that n-3 PUFA will have "drug" like effects, and this high expectation may have led to the inconsistent evidence in the literature. The inconsistency in the literature may be related to varying doses of n-3 PUFA, sources of n-3 PUFA (food vs. supplement; plant vs. marine), type of n-3 PUFA (mixture vs. purified), trial duration, population characteristics, sample size, and genetic variation. For future research, there is a need to distinguish between primary and secondary prevention, and to focus RCTs on primary prevention of chronic diseases by n-3 PUFA which is lacking in the literature.

Omega-3 polyunsaturated fatty acids in the treatment of non-alcoholic fatty liver disease: An umbrella systematic review and meta-analysis.

There has been conflicting evidence from meta-analyses on the effect of polyunsaturated fatty acids (PUFA) on non-alcoholic fatty liver disease (NAFLD). Therefore, in this umbrella meta-analysis, we are evaluating whether omega-3 PUFA supplementation has any benefit in treating NAFLD. Electronic databases such as PubMed, Web of Science, Scopus, Embase and Google Scholar were assessed to October 2022. This meta-analysis included all meta-analyses that examined the effect of PUFAs on liver fat and liver function tests [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)]. Meta-analysis was conducted using a random effects model. Subgroup analyses and sensitivity analyses were also performed. In total, eight articles involving 6,561 participants met the eligibility criteria. Advantageous impacts PUFA supplementation were observed on ALT (ESWMD = -6.72 IU/L; 95% CI: -8.61, -4.84; p< 0.001, and ESSMD = -0.52 IU/L; 95% CI: -0.84, -0.20, p< 0.001), AST (ESWMD = -3.73 IU/L, 95% CI: -5.93, -1.53, p< 0.001, and ESSMD = -0.65 IU/L; 95% CI: -1.08, -0.22, p= 0.003), GGT levels (ESWMD = -4.20 IU/L, 95% CI: -6.85, -1.55, p= 0.002), and liver fat (ESWMD = -5.16; 95% CI: -8.49, -1.82, p< 0.001). Intervention with omega-3 PUFAs improves ALT, AST, GGT, and liver fat in patients with NAFLD. Thus, omega-3 PUFAs could be considered as a therapeutic option in the treatment of NAFLD.

Impacts of Eccentric Resistance Exercise on DNA Methylation of Candidate Genes for Inflammatory Cytokines in Skeletal Muscle and Leukocytes of Healthy Males.

Physical inactivity and a poor diet increase systemic inflammation, while chronic inflammation can be reduced through exercise and nutritional interventions. The mechanisms underlying the impacts of lifestyle interventions on inflammation remain to be fully explained; however, epigenetic modifications may be critical. The purpose of our study was to investigate the impacts of eccentric resistance exercise and fatty acid supplementation on DNA methylation and mRNA expression of TNF and IL6 in skeletal muscle and leukocytes. Eight non-resistance exercise-trained males completed three bouts of isokinetic eccentric contractions of the knee extensors. The first bout occurred at baseline, the second occurred following a three-week supplementation of either omega-3 polyunsaturated fatty acid or extra virgin olive oil and the final bout occurred after eight-weeks of eccentric resistance training and supplementation. Acute exercise decreased skeletal muscle TNF DNA methylation by 5% (p = 0.031), whereas IL6 DNA methylation increased by 3% (p = 0.01). Leukocyte DNA methylation was unchanged following exercise (p > 0.05); however, three hours post-exercise the TNF DNA methylation decreased by 2% (p = 0.004). In skeletal muscle, increased TNF and IL6 mRNA expression levels were identified immediately post-exercise (p < 0.027); however, the leukocyte mRNA expression was unchanged. Associations between DNA methylation and markers of exercise performance, inflammation and muscle damage were identified (p < 0.05). Acute eccentric resistance exercise is sufficient to induce tissue-specific DNA methylation modifications to TNF and IL6; however, neither eccentric training nor supplementation was sufficient to further modify the DNA methylation.

Effects of Omega-3 Fatty Acids Supplementation on Serum Lipid Profile and Blood Pressure in Patients with Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The purpose of this study was to explore the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation on serum lipid profile and blood pressure in patients with metabolic syndrome. We searched PubMed, Web of Science, Embase, and the Cochrane library from database inception to 30 April 2022. This meta-analysis included eight trials with 387 participants. We found that supplementation of n-3 PUFAs has no significant reduction in TC level (SMD = -0.02; 95% CI: -0.22 ~ 0.18, I2 = 23.7%) and LDL-c level in serum (SMD = 0.18; 95% CI: -0.18 ~ 0.53, I2 = 54.9%) of patients with metabolic syndrome. Moreover, we found no significant increase in serum high-density lipoprotein cholesterol level (SMD = 0.02; 95% CI: -0.21 ~ 0.25, I2 = 0%) in patients with metabolic syndrome after consuming n-3 PUFAs. In addition, we found that n-3 PUFAs can significantly decrease serum triglyceride levels (SMD= -0.39; 95% CI: -0.59 ~ -0.18, I2 = 17.2%), systolic blood pressure (SMD = -0.54; 95% CI: -0.86 ~ -0.22, I2 = 48.6%), and diastolic blood pressure (SMD = -0.56; 95% CI: -0.79 ~ 0.33, I2 = 14.0%) in patients with metabolic syndrome. The results from the sensitivity analysis confirmed that our results were robust. These findings suggest that n-3 PUFA supplementation may serve as a potential dietary supplement for improving lipids and blood pressure in metabolic syndrome. Given the quality of the included studies, further studies are still needed to verify our findings.

Dihomo-γ-Linolenic Acid (20:3n-6)-Metabolism, Derivatives, and Potential Significance in Chronic Inflammation.

Dihomo-γ-linolenic acid (DGLA) has emerged as a significant molecule differentiating healthy and inflamed tissues. Its position at a pivotal point of metabolic pathways leading to anti-inflammatory derivatives or via arachidonic acid (ARA) to pro-inflammatory lipid mediators makes this n-6 polyunsaturated fatty acid (PUFA) an intriguing research subject. The balance of ARA to DGLA is probably a critical factor affecting inflammatory processes in the body. The aim of this narrative review was to examine the potential roles of DGLA and related n-6 PUFAs in inflammatory conditions, such as obesity-associated disorders, rheumatoid arthritis, atopic dermatitis, asthma, cancers, and diseases of the gastrointestinal tract. DGLA can be produced by cultured fungi or be obtained via endogenous conversion from γ-linolenic acid (GLA)-rich vegetable oils. Several disease states are characterized by abnormally low DGLA levels in the body, while others can feature elevated levels. A defect in the activity of ∆6-desaturase and/or ∆5-desaturase may be one factor in the initiation and progression of these conditions. The potential of GLA and DGLA administrations as curative or ameliorating therapies in inflammatory conditions and malignancies appears modest at best. Manipulations with ∆6- and ∆5-desaturase inhibitors or combinations of long-chain PUFA supplements with n-3 PUFAs could provide a way to modify the body's DGLA and ARA production and the concentrations of their pro- and anti-inflammatory mediators. However, clinical data remain scarce and further well-designed studies should be actively promoted.

Omega-3 Polyunsaturated Fatty Acids Supplements and Cardiovascular Disease Outcome: A Systematic Review and Meta-Analysis on Randomized Controlled Trials.

Many meta-analyses and randomized controlled trials (RCTs) on the use of Omega-3 supplements for cardiovascular disease (CVD) have come to different outcomes. Besides, previous meta-analyses have missed some key RCTs on this topic. PubMed, EMBASE, Cochrane Library and Web of Science were manually searched for eligible RCTs on Omega-3 polyunsaturated fatty acids (PUFA) use for CVD. Risk estimates of each relevant outcome were calculated as a hazard ratio (HR) with 95% confidence interval (95% CI) using the random-effects model. Subgroup analysis was conducted according to the main characteristics of the population, sensitivity analysis would be performed if there was significant heterogeneity among analyses on relevant outcomes. Statistical heterogeneity was assessed using chi-square tests and quantified using I-square statistics. Nineteen eligible RCTs incorporating 116,498 populations were included. Omega-3 PUFA supplementation could not significantly improve the outcomes of major adverse cardiovascular events (MACE) (HR: 0.98, 95% CI: 0.91-1.06), myocardial infarction (MI) (HR: 0.86, 95% CI: 0.70-1.05), coronary heart disease (CHD) (HR: 0.90, 95% CI: 0.80-1.01), stroke (HR: 1.00, 95% CI: 0.91-1.10), SCD (sudden cardiac death) (HR: 0.90, 95% CI: 0.80-1.02), all-cause mortality (HR: 0.96, 95% CI: 0.89-1.04), hospitalization (HR: 0.99, 95% CI: 0.81-1.20), hospitalization for all heart disease (HR: 0.91, 95% CI: 0.83-1.00), hospitalization for heart failure (HR: 0.97, 95% CI: 0.91-1.04). Although omega-3 PUFA significantly reduced revascularization (HR: 0.90, 95% CI: 0.81-1.00) and cardiovascular mortality (CV mortality) (HR: 0.91, 95% CI: 0.85-0.97), risk for atrial fibrillation (AF) was also increased (HR: 1.56, 95% CI: 1.27-1.91). Subgroup analysis results kept consistent with the main results. Omega-3 PUFA supplementation could reduce the risk for CV mortality and revascularization, it also increased the AF incidence. No obvious benefits on other CVD outcomes were identified. Overall, potential CVD benefits and harm for AF should be balanced when using omega-3 PUFA for patients or populations at high risk.

A review and evaluation of study design considerations for omega-3 fatty acid supplementation trials in physically trained participants.

Long-chain omega-3 polyunsaturated fatty acid (LC n-3 PUFA) supplements, rich in eicosapentaenoic acid and/or docosahexaenoic acid, are increasingly being recommended within athletic institutions. However, the wide range of doses, durations and study designs implemented across trials makes it difficult to provide clear recommendations. The importance of study design characteristics in LC n-3 PUFA trials has been detailed in cardiovascular disease research, and these considerations may guide LC n-3 PUFA study design in healthy cohorts. This systematic review examined the quality of studies and study design considerations used in evaluating the evidence for LC n-3 PUFA improving performance in physically trained adults. SCOPUS, PubMed and Web of Science electronic databases were searched to identify studies that supplemented LC n-3 PUFA in physically trained participants. Forty-six (n = 46) studies met inclusion. Most studies used a randomised control design. Risk of bias, assessed using the design-appropriate Cochrane Collaboration tool, revealed that studies had a predominant judgment of 'some concerns', 'high risk' or 'moderate risk' in randomised controlled, randomised crossover or non-randomised studies, respectively. A custom five-point quality assessment scale demonstrated that no study satisfied all recommendations for LC n-3 PUFA study design. This review has highlighted that the disparate range of study designs is likely contributing to the inconclusive state of outcomes pertaining to LC n-3 PUFA as a potential ergogenic aid. Further research must adequately account for the specific LC n-3 PUFA study design considerations, underpinned by a clear hypothesis, to achieve evidence-based dose, duration and composition recommendations for physically trained individuals.

Omega-3 polyunsaturated fatty acids ameliorate PM2.5 exposure induced lung injury in mice through remodeling the gut microbiota and modulating the lung metabolism.

Short-term or long-term exposure to fine particulate matter (PM2.5) is related to increased incidences of respiratory diseases. This study aimed to investigate the influences of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) supplementation on oxidative stress, inflammation, lung metabolic profile, and gut microbiota in PM2.5-induced lung injury mice. Mice were divided into four groups (n = 15, per group): two unsupplemented groups, control group and PM2.5 group, and two supplemented groups with ω-3 PUFAs, ω-3 PUFAs group, and ω-3 PUFAs + PM2.5 group. Mice in the supplemented groups were placed on an ω-3 PUFAs-enriched diet (ω-3 PUFAs, 21g/kg). During the 5th to 6th week of dietary supplementation, mice were exposed to PM2.5 by intra-tracheal instillation. ω-3 PUFAs ameliorate lung histopathological injury, reduce inflammatory responses and oxidative stress, affect lung metabolite profile, and modulate gut microbiota in PM2.5-induced lung injury mice. Thus, supplementary ω-3 PUFAs showed effectiveness in attenuation of PM2.5-induced lung injury, indicating that the interventions exhibited preventive and therapeutic potential.

Effects of polyunsaturated fatty acid supplementation on plasma and follicular fluid resolvin D1 concentration and mRNA abundance in granulosa cells in ewes.

The aim of this experiment was to evaluate the effect of increasing dietary omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation on plasma and follicular fluid resolvin D1 (RvD1) concentration and the mRNA expression of genes related to RvD1 production, inflammatory response, oxidative stress, hormone receptors and production, and free fatty acid receptors in the granulosa cells of ewes. Dorset × Hampshire ewes (n = 24) aged 2 to 4 yr and with an initial body weight (BW) of 84.08 ± 13.18 kg were blocked by body condition score (BCS) and BW, and randomly assigned to 12 pens. Each pen within each block was randomly assigned to one of three treatments: 1) diet without fatty acid supplementation (control), 2) diet with 0.5% n-3 PUFA supplementation (PUFA0.5), and 3) diet with 1% n-3 PUFA supplementation (PUFA1). BW, BCS, and blood samples were obtained on day 1 and every 21 d for 3 mo. Ewes were then synchronized, superstimulated, and ovariectomized. Antral follicles were aspirated to evaluate RvD1 concentration in follicular fluid, and granulosa cells were used to determine mRNA abundance. Data were analyzed as a randomized complete block design using a mixed model (MIXED or GLIMMIX with log as a link function when data presented a nonnormal distribution). A polynomial effect of treatments was used to analyze RvD1 concentration and mRNA expression when there was no interaction. In addition, the correlation between plasma and follicular fluid RvD1 concentration was evaluated. We found no differences in BW (P = 0.28) and BCS (P = 0.29) between treatments. The concentration of RvD1 in plasma and follicular fluid linearly increased (P = 0.03) and tended to increase (P = 0.06) concomitantly to increasing PUFA supplementation. Plasma and follicular fluid RvD1 concentrations were positively correlated (r = 0.61; P < 0.01). The abundance of GPX1 and GPR32 mRNA tended to increase linearly with increasing PUFA supplementation (P = 0.06). In addition, PUFA supplementation linearly decreased and tended to decrease IL-1β and COX-2 mRNA abundance (P = 0.01 and P = 0.06, respectively). In conclusion, the correlation between plasma and follicular fluid RvD1 concentration indicates a relationship between both compartments. Also, the decrease of IL-1β and the increase of GPX1 mRNA abundance after PUFA supplementation could have beneficial effects on follicle development.

PUFA supplements to improve diarrhea, fecal consistency, and disease resilience in neonatal and preweaning calves

The flaxseed oil (FSO) rich in polyunsaturated fatty acids (PUFA) were supplemented orally to ten male and female neonatal calves from day 6 of birth to day 28 to improve resilience to disease incidences (TG) and compared to calves reared without PUFA supplement (CG). The PUFA supplementation in liquid form was discontinued on day 29 and fed as bolus consisting of 25 g of ground flaxseed and 25 g of jaggery until day 90. The total dry matter intake in cluding milk solids in neonata calves was 400 g in CG and 428 g in TG (P=0.38). Digestible DMI, CP and energy intake in male and female calves of TGs was significantly (P&lt; 0.05) higher the CG. However, the body weight gain in calves during neonatal (P=0.08) and preweaning (P=0.14) age was comparable between groups. The serum IgG were 30 mg/mL on day 2 but higher in calves in TGs on day 7 (P=0.08) and day 14 (P=0.07)after birth but comparable in subsequent period until day 30 after birth. Calves resilience to diarrhea, pyrexia, anorexia, skin infection, profused lacrimation, navel ill, muzzle keratinization, umbilical hernia, fecal consistency (FC), and egg count (FEC) were examined. PUFA supplementation reduced the disease risk rate in TG by 42% (P&lt; 0.001) and diarrhea by three folds compared to CG. Haemoglobin, erythrocytes, and lymphocytes improved significantly from day 30 after birth. The intervention was recommended to reduce calf mortality and imrpoved health and body weight gain during neonatal and preweaning age.

The effect of n-3 polyunsaturated fatty acid supplementation on cognitive function outcomes in the elderly depends on the baseline omega-3 index.

Both epidemiological and preclinical studies have shown the benefits of n-3 polyunsaturated fatty acid (n-3 PUFA) on dementia and cognitive impairment, yet the results of clinical randomized controlled trials (RCTs) performed to date are conflicting. The difference in the baseline omega-3 index (O3i) of subjects is a potential cause for this disparity, yet this is usually ignored. The present meta-analysis aimed to evaluate the effect of n-3 polyunsaturated fatty acid (n-3 PUFA) on cognitive function in the elderly and the role of baseline O3i. A systematic literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science up to June 27th, 2023. The mean changes in the mini-mental state examination (MMSE) score were calculated as weighted mean differences by using a fixed-effects model. Fifteen random controlled trials were included in the meta-analysis. Pooled analysis showed that n-3 PUFA supplementation did not significantly improve the MMSE score (WMD = 0.04, [-0.08, 0.16]; Z = 0.62, P = 0.53; I2 = 0.00%, P(I2) = 0.49). Out of the 15 studies included in the meta-analysis, only 7 reported O3i at baseline and outcome, so only these 7 articles were used for subgroup analysis. Subgroup analysis showed that the MMSE score was significantly improved in the higher baseline O3i subgroup (WMD = 0.553, [0.01, 1.095]; I2 = 0.00%, P(I2) = 0.556) and higher O3i increment subgroup (WMD = 0.525, [0.023, 1.026]; I2 = 0.00%, P(I2) = 0.545). The overall effect demonstrated that n-3 PUFA supplementation exerted no improvement on global cognitive function. However, a higher baseline O3i and higher O3i increment were associated with an improvement in cognitive function in the elderly.

Effects of n-3 polyunsaturated fatty acid supplementation on quadriceps weakness immediately after total knee arthroplasty: a pilot, randomized, open-label clinical trial.

[Purpose] Severe quadriceps weakness immediately after total knee arthroplasty can be problematic. The n-3 long-chain polyunsaturated fatty acids have antioxidant and anti-inflammatory effects against ischemia-reperfusion injury, whereas n-6 long-chain polyunsaturated fatty acids exert pro-inflammatory effects, thereby promoting ischemia-reperfusion injury. [Participants and Methods] We explored the efficacy of preoperative n-3 long-chain polyunsaturated fatty acid supplementation against early quadriceps weakness among 20 patients scheduled for total knee arthroplasty (intervention group, n=10; control group, n=10). The intervention group received 645 mg of eicosapentaenoic acid) and 215 mg of docosahexaenoic acid daily for 30 days preoperatively. Serum eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid levels were measured preoperatively. We compared serum derivatives of reactive oxygen metabolites as oxidative stress biomarkers, knee circumference, thigh volume, knee pain during the quadriceps strength test, and quadriceps strength preoperatively and 4 days postoperatively to quantify the change. [Results] Preoperative n-3 long-chain polyunsaturated fatty acid supplementation significantly increased the (eicosapentaenoic acid+docosahexaenoic acid)/arachidonic acid ratio in the intervention group. A significantly lower increase in quadriceps weakness was exhibited in the intervention group than in the control group. However, changes in oxidative stress, knee/thigh swelling, and knee pain during strength testing did not significantly differ between the two groups. [Conclusion] Preoperative n-3 long-chain polyunsaturated fatty acid supplementation exhibited beneficial effects on quadriceps weakness immediately after total knee arthroplasty.

Применение омега-3 полиненасыщенных жирных кислот в качестве прегравидарной подготовки

Aim: to study the effect of omega-3 polyunsaturated fatty acids (PUFA) supplement on the balance of fatty acids in female pregravidar preparation. Patients and Methods: the study included 42 female patients of the reproductive age who were planning pregnancy in the nearest future. The main group consisted of 24 female patients who took a drug containing omega-3 PUFA 585 mg for the pregravidar preparation. The control group included 18 female patients who took drugs containing folic acid 400 μg in a daily dose, iodine 200 μg, vitamin D 2000 U. The follow-up period of female patients and results control of the laboratory parameters during the treatment was 3 months. Then, the follow-up was based on the results of the reproductive performance implementation in a year. Results: during the therapy, omega-3 PUFA intake leaded to a slight increase of the fatty acids (FA) content, i.e., to the normalization of this indicator, which didn't not require constant control of the FA level and did not limit the time of use. Besides, when omega-3 PUFA was prescribed, the frequency of inevitable miscarriage might decrease (OR 2.6, 95% CI 1.2–14.7), however, this statement requires further study and confirmation in a larger number of female patients. Conclusion: the additional prescription of omega-3 PUFA for the pregravidar preparation has a positive effect. At the same time, routine determination of the fatty acids level and its control during the intake is not required before the prescription. The intake of omega-3 PUFA during pregnancy and in the early neonatal period is important for the subsequent normal functioning of the child's body. KEYWORDS: pregravidar preparation, miscarriage, polyunsaturated fatty acids, omega-3 PUFA, fatty acids, eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid, oleic acid, nervonic acid, vitamin E, folic acid. FOR CITATION: Ilyina I.Yu., Dobrokhotova Yu.E. omega-3 polyunsaturated fatty acids as a pregravidar preparation. Russian Journal of Woman and Child Health. 2023;6(3):233–240 (in Russ.). DOI: 10.32364/2618-8430-2023-6-3-3.

The Influence of n-3PUFA Supplementation on Muscle Strength, Mass, and Function: A Systematic Review and Meta-Analysis.

The effects of omega 3 polyunsaturated fatty acids (n-3PUFA) supplementation on skeletal muscle are currently unclear. The purpose of this systematic review was to synthesize all available evidence regarding the influence of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. Four databases were searched (Medline, Embase, Cochrane CENTRAL, and SportDiscus). Predefined eligibility criteria were determined according to Population, Intervention, Comparator, Outcomes, and Study Design. Only peer-reviewed studies were included. The Cochrane RoB2 Tool and the NutriGrade approach were used to access risk of bias and certainty in evidence. Effect sizes were calculated using pre-post scores and analyzed using a three-level, random-effects meta-analysis. When sufficient studies were available, subanalyses were performed in the muscle mass, strength, and function outcomes according to participant's age (<60 or ≥60 years), supplementation dosage (<2 or ≥2 g/day), and training intervention ("resistance training" vs. "none or other"). Overall, 14 individual studies were included, total 1443 participants (913 females; 520 males) and 52 outcomes measures. Studies had high overall risk of bias and consideration of all NutriGrade elements resulted in a certainty assessment of moderate meta-evidence for all outcomes. n-3PUFA supplementation had no significant effect on muscle mass (standard mean difference [SMD] = 0.07 [95% CI: -0.02, 0.17], P = 0.11) and muscle function (SMD = 0.03 [95% CI: -0.09, 0.15], P = 0.58), but it showed a very small albeit significant positive effect on muscle strength (SMD = 0.12 [95% CI: 0.006, 0.24], P = 0.04) in participants when compared with placebo. Subgroup analyses showed that age, supplementation dose, or cosupplementation alongside resistance training did not influence these responses. In conclusion, our analyses indicated that n-3PUFA supplementation may lead to very small increases in muscle strength but did not impact muscle mass and function in healthy young and older adults. To our knowledge, this is the first review and meta-analysis investigating whether n-3PUFA supplementation can lead to increases in muscle strength, mass, and function in healthy adults. Registered protocol: doi.org/10.17605/OSF.IO/2FWQT.

Omega-3 polyunsaturated fatty acids and corneal nerve health: Current evidence and future directions.

Corneal nerves play a key role in maintaining ocular surface integrity. Corneal nerve damage, from local or systemic conditions, can lead to ocular discomfort, pain, and, if poorly managed, neurotrophic keratopathy. Omega-3 polyunsaturated fatty acids (PUFAs) are essential dietary components that play a key role in neural development, maintenance, and function. Their potential application in modulating ocular and systemic inflammation has been widely reported. Omega-3 PUFAs and their metabolites also have neuroprotective properties and can confer benefit in neurodegenerative disease. Several preclinical studies have shown that topical administration of omega-3 PUFA-derived lipid mediators promote corneal nerve recovery following corneal surgery. Dietary omega-3 PUFA supplementation can also reduce corneal epithelial nerve loss and promote corneal nerve regeneration in diabetes. Omega-3 PUFAs and their lipid mediators thus show promise as therapeutic approaches to modulate corneal nerve health in ocular and systemic disease. This review discusses the role of dietary omega-3 PUFAs in maintaining ocular surface health and summarizes the possible applications of omega-3 PUFAs in the management of ocular and systemic conditions that cause corneal nerve damage. In examining the current evidence, this review also highlights relatively underexplored applications of omega-3 PUFAs in conferring neuroprotection and addresses their therapeutic potential in mediating corneal nerve regeneration.

The impact of omega-3 polyunsaturated fatty acid supplementation on the cardiovascular response to low-intensity exercise, hypoxia and heat exposure: a randomized controlled trial

The impact of omega-3 polyunsaturated fatty acid supplementation on the cardiovascular response to low-intensity exercise, hypoxia and heat exposure: a randomized controlled trial

Effect of dietary omega-3 polyunsaturated fatty acids supplementation of Astyanax lacustris males on semen quality

Abstract This study aimed to verify whether the inclusion of omega-3 polyunsaturated fatty acids (PUFAs-ô3) in the diet of Astyanax lacustris males improves seminal quality. Four hundred fish were arranged in 20 boxes of 180 L in the recirculation system. These were fed with isoprotein diets (32% CP), until apparent satiation, with four levels of marine fish oil rich in PUFAs-ô3 inclusion (In% = 0, 3, 6, and 9), for 105 days. After, males were hormonally induced to spermiation, and semen was collected after 226 ATUs. Parameters evaluated were osmolality, seminal volume and color, spermatic concentration, sperm morphology, membrane integrity and, sperm motility (total and progressive motility, velocity curvilinear, straight line and average path, linearity and rectilinearity coefficients, trajectory oscillation, head lateral displacement amplitude, and cross-beat frequency). Seminal volume was greater in the In-0 and In-3 groups. Inclusion of PUFAs-ô3 positively influenced the kinetic parameters, as treatment with 6% and 9% of inclusion fish oil resulted in higher values for most of these parameters and did not differ statistically from each other. Thus, it is concluded that the addition of PUFAs-ô3 to the feed of breeders significantly improved the seminal quality of A. lacustris males.

Endogenously Synthesized n-3 fatty Acids in fat-1 Transgenic Mice Suppresses B Cell Activation

n-3 Polyunsaturated fatty acids (PUFAs) have been suggested as a preventive or therapeutic strategy for autoimmune or inflammatory diseases via the modulation of the activation, differentiation, and effector functions of various immune cells, especially T cells and macrophages. Despite the importance of B cells in the pathogenesis of autoimmune diseases, few studies have demonstrated their effect on B cells. In this study, we investigated the possible effects of n-3 PUFAs on B cell activation, differentiation, and isotype switching in fat-1 transgenic mice, which can convert n-6 PUFAs to n-3 PUFAs via n-3 desaturase derived from Caenorhabditis elegans. Fat-1 mice were fed a corn oil-rich diet for at least 4 weeks to increase the probability of converting n-6 PUFAs to n-3 PUFAs. Splenic B cells were then isolated, followed by stimulation with Toll-like receptor 4 or B cell receptor (BCR). Our results showed that increased n-3 PUFA levels in B cells by fat-1 overexpression inhibited B cell proliferation, cytokine secretion, such as interleukin (IL)-6, IL-10, tumor necrosis factor-α, plasma cell differentiation, and Ig isotype switching/secretion. These effects are possibly due to the suppression of Syk, Src, and AKT activation in B cells from fat-1 mice, as well as NF-κB. Collectively, our results suggest that fat-1 expression attenuates B cell responses, and n-3 PUFA supplementation can be a possible strategy to treat pathological conditions in which B cells play a key role.

Long-chain polyunsaturated fatty acid supplementation increases levels in red blood cells and reduces the prevalence and severity of squamous gastric ulcers in exercised Thoroughbreds.

To assess the relationship between plasma and RBC fatty acid composition and incidence and severity of squamous gastric ulcers when altered by short-chain (SC) or long-chain (LC) polyunsaturated fatty acid (PUFA) supplementation. 13 fit Thoroughbred horses in training. Horses were evaluated by gastroscopy for squamous ulcer score, gastric pH, and blood fatty acid composition prior to supplementation (UNSUPP) and after 3 months of supplementation with a corn-flax oil blend of alpha-linolenic acid and linoleic acid (SC-PUFA) or a gamma-linolenic acid (GLA)-fish oil blend of GLA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA; LC-PUFA) in a crossover design. Prior to gastroscopy and blood collection, horses performed a 4,600-m standardized exercise test on the racetrack as a stressor. Three months of supplementation with LC-PUFAs increased RBC levels of GLA, dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA), EPA, and DHA, and reduced severe ulcer prevalence (38% UNSUPP vs 8% LC-PUFA with a severe ulcer score of grade 3 to 4). Short-chain PUFA supplementation did not effectively elevate RBC GLA, DGLA, AA, EPA, or DHA and severe ulcer incidence was not different (38% UNSUPP vs 23% SC-PUFA with a severe ulcer score of grade 3 to 4). Lower levels of RBC GLA, DGLA, AA, and EPA correlated with severe squamous gastric ulceration (grade 3 to 4). Equine gastric ulcer syndrome is prevalent in high-performance horses and is a concern to owners and trainers. Long-chain PUFA supplementation increased levels of GLA, DGLA, AA, EPA, and DHA, unlike SC-PUFA supplementation, and was associated positively with prevention or resolution of severe squamous gastric ulceration. Further studies are needed to evaluate different management styles and exercise intensities.

The high-dose fish oil supplementation increased Mfsd2a expression without altering DHA levels in the retina of healthy mice

• The healthy retina requires daily omega-3 PUFA supplementation. • High-dose FO supplementation can be more beneficial than currently recommended doses. • High-dose FO supplementation alters lipid content in the eye. • High-dose FO supplementation has the potential to fortify retinal blood vessels. The recommended fish oil (FO) supplementation doses often yield low omega-3 polyunsaturated fatty acids (PUFAs) tissue bioavailability, and higher doses (up to 10 g per day) have been increasingly recommended. However, the exact effects of such FO supplementation on the healthy retina and retinal pigmented epithelium (RPE) are unknown. Our study showed that the high dose FO treatment did not imbalance the rigorous docosahexaenoic acid (DHA, C22:6n3) homeostasis in the retina and RPE in the three-month-old female B6/SLJ mice. Instead, we have found the significant increase in the expression of Mfsd2a, the main DHA transporter. Mfsd2a is also an essential regulator of blood vessel transcytosis and the decrease in Mfsd2a expression can be a risk factor for developing leaky blood vessels. Therefore, the high-dose FO supplementation emerges as the prophylactic fortifier of the retinal blood vessels.