Restoring retinal polyunsaturated fatty acid balance and retina function by targeting ceramide in AdipoR1-deficient mice.

Mutations in the adiponectin receptor 1 gene (AdipoR1) lead to retinitis pigmentosa and are associated with age-related macular degeneration. This study explores the effects of AdipoR1 gene deficiency in mice, revealing a striking decline in ω3 polyunsaturated fatty acids (PUFA), an increase in ω6 fatty acids, and elevated ceramides in the retina. The AdipoR1 deficiency impairs peroxisome proliferator-activated receptor α signaling, which is crucial for FA metabolism, particularly affecting proteins associated with FA transport and oxidation in the retina and retinal pigmented epithelium. Our lipidomic and proteomic analyses indicate changes that could affect membrane composition and viscosity through altered ω3 PUFA transport and synthesis, suggesting a potential influence of AdipoR1 on these properties. Furthermore, we noted a reduction in the Bardet-Biedl syndrome proteins, which are crucial for forming and maintaining photoreceptor outer segments that are PUFA-enriched ciliary structures. Diminution in Bardet-Biedl syndrome-proteins content combined with our electron microscopic observations raises the possibility that AdipoR1 deficiency might impair ciliary function. Treatment with inhibitors of ceramide synthesis led to substantial elevation of ω3 LC-PUFAs, alleviating photoreceptor degeneration and improving retinal function. These results serve as the proof of concept for a ceramide-targeted strategy to treat retinopathies linked to PUFA deficiency, including age-related macular degeneration.

Key questions and gaps in understanding adipose tissue macrophages and early-life metabolic programming.

The global obesity epidemic, with its associated comorbidities and increased risk of early mortality, underscores the urgent need for enhancing our understanding of the origins of this complex disease. It is increasingly clear that metabolism is programmed early in life and that metabolic programming can have life-long health consequences. As a critical metabolic organ sensitive to early-life stimuli, proper development of adipose tissue (AT) is crucial for life-long energy homeostasis. Early-life nutrients, especially fatty acids (FAs), significantly influence the programming of AT and shape its function and metabolism. Of growing interest are the dynamic responses during pre- and postnatal development to proinflammatory omega-6 (n6) and anti-inflammatory omega-3 (n3) FA exposures in AT. In the US maternal diet, the ratio of "pro-inflammatory" n6- to "anti-inflammatory" n3-FAs has grown dramatically due to the greater prevalence of n6-FAs. Notably, AT macrophages (ATMs) form a significant population within adipose stromal cells, playing not only an instrumental role in AT formation and maintenance but also acting as key mediators of cell-to-cell lipid and cytokine signaling. Despite rapid advances in ATM and immunometabolism fields, research has focused on responses to obesogenic diets and during adulthood. Consequently, there is a significant gap in identifying the mechanisms contributing metabolic health, especially regarding lipid exposures during the establishment of ATM physiology. Our review highlights the current understanding of ATM diversity, their critical role in AT, their potential role in early-life metabolic programming, and the broader implications for metabolism and health.

Associations of plasma omega-6 and omega-3 fatty acids with overall and 19 site-specific cancers: A population-based cohort study in UK Biobank.

Previous epidemiological studies on the associations between polyunsaturated fatty acids (PUFAs) and cancer incidence have been inconsistent. We investigated the associations of plasma omega-3 and omega-6 PUFAs with the incidence of overall and 19 site-specific cancers in a large prospective cohort. 253,138 eligible UK Biobank participants were included in our study. With a mean follow-up of 12.9 years, 29,838 participants were diagnosed with cancer. The plasma levels of omega-3 and omega-6 PUFAs were expressed as percentages of total fatty acids (omega-3% and omega-6%). In our main models, both omega-6% and omega-3% were inversely associated with overall cancer incidence (HR per SD = 0.98, 95% CI = 0.96-0.99; HR per SD = 0.99, 95% CI = 0.97-1.00; respectively). Of the 19 site-specific cancers available, 14 were associated with omega-6% and five with omega-3%, all indicating inverse associations, with the exception that prostate cancer was positively associated with omega-3% (HR per SD = 1.03, 95% CI = 1.01-1.05). Our population-based cohort study in UK Biobank indicates small inverse associations of plasma omega-6 and omega-3 PUFAs with the incidence of overall and most site-specific cancers, although there are notable exceptions, such as prostate cancer.

Employing Bidirectional Two-Sample Mendelian Randomization Analysis to Verify the Potential of Polyunsaturated Fatty Acid Levels in the Prevention of Pancreatic Cancer.

Polyunsaturated fatty acids (PUFAs), specifically Omega-3 (FAω3) and docosahexaenoic acid (DHA), have been studied for their potential role in modulating pancreatic cancer (PC) risk. Although observational studies suggest a beneficial effect in reducing this risk, their findings are often limited by confounding variables and issues of reverse causation. This study used a two-way two-sample Mendelian randomization (MR) method to test the hypothesized genetic causal relationship between PUFAs and PC risk. Data from an extensive genome-wide association study (GWAS) were analyzed, focusing on FAω3 and FAω6 levels, their ratios, and DHA as variables and PC incidence as outcomes. This relationship was comprehensively evaluated using related MR methods, such as inverse variance weighting (IVW), MR Egger, and weighted median (WM). This study finds a significant negative correlation between FAω3 and DHA levels and PC risk, while FAω6 levels show no significant correlation. Interestingly, the ratio of FAω6 to FAω3 was positively associated with increased risk of PC. Neither the MR Egger nor the MR-PRESSO tests detected significant pleiotropy, nor did the Cochrane's Q test show significant heterogeneity. Leave-one-out analyzes further confirmed the robustness of these results. Using MR analysis of two samples, this study provides genetic causal evidence that FAω3 and DHA levels reduce the risk of PC, whereas the ratio of FAω6 to FAω3 increases the risk of PC. These insights highlight the potential utility of supplementing FAω3 and DHA or altering PUFAs in developing PC prevention strategies.

Plasma Levels of Polyunsaturated Fatty Acids and Adverse Kidney Outcomes.

RATIONALE & OBJECTIVE: Many studies have reported polyunsaturated fatty acids (PUFA) as significant predictors of cardiovascular disease, but little is known about the relationship between PUFA levels and chronic kidney disease (CKD). This study explored this relationship among individuals with and without CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 73,419 participants without CKD (cohort 1) and 6,735 participants with CKD (cohort 2) in the UK Biobank Study, with PUFA levels measured between 2007 and 2010. EXPOSURE: Percentage of plasma PUFA, omega-3 fatty acid (FA), omega-6 FA, docosahexaenoic acid (DHA), and linoleic acid relative to total FA. OUTCOME: Incident CKD for cohort 1 and incident kidney failure requiring replacement therapy (KFRT) for cohort 2. ANALYTICAL APPROACH: Cox proportional hazards regression analyses, including a cause-specific competing risk model. RESULTS: In cohort 1, individuals with higher quartiles of plasma PUFA levels had healthier lifestyles and fewer comorbidities. During 841,007 person-years of follow-up (median 11.9 years), incident CKD occurred in 4.5% of participants (incidence rate, 39.1 per 10,000 person-years). For incident CKD in cohort 1, the adjusted cause-specific hazard ratios for quartiles 2, 3, and 4 were 0.83 (95% CI, 0.75-0.92), 0.85 (95% CI, 0.76-0.96), 0.71 (95% CI, 0.62-0.82), respectively, compared with quartile 1. This inverse relationship was consistently observed for all PUFA types. In cohort 2, although total PUFA levels were not associated with KFRT, higher PUFA subtype levels of DHA were associated with a lower risk of KFRT. LIMITATIONS: Observational design and limited generalizability to individuals with higher disease severity; no data on eicosapentaenoic acid. CONCLUSIONS: Among individuals without CKD, higher plasma PUFA levels and all 4 PUFA components were associated with a lower risk of incident CKD. In individuals with CKD, only the omega-3 component of PUFA, DHA, was associated with a lower risk of KFRT. PLAIN-LANGUAGE SUMMARY: Low amounts of polyunsaturated fatty acids (PUFA) in the blood are suspected of increasing the chances of heart disease, but it is not known whether the PUFA relates to kidney disease occurrence. In a large group without kidney disease in the United Kingdom, people with higher levels of PUFA in their blood tended to have a lower risk of developing kidney disease compared to those with lower PUFA levels. This relationship was consistently observed for all PUFA types. However, in the group with kidney disease, only higher levels of docosahexaenoic acid, a subtype of PUFAs, were associated with a lower risk of developing severe kidney problems that required kidney replacement therapy. These findings suggest that higher levels of PUFA, found in certain healthy fats, might protect against the development of kidney disease in the general population. As kidney function declines, only the docosahexaenoic acid, a subtype of PUFA, appears to be associated with preserved kidney function.

Improvements in markers of inflammation and coagulation potential following a 5-day high-fat diet rich in cottonseed oil vs. Olive oil in healthy males.

Low-grade inflammation is believed to be a risk factor for chronic diseases and is nutritionally responsive. Cottonseed oil (CSO), which is rich in n-6 polyunsaturated fats, has been shown to lower cholesterol and other chronic disease risk factors. The purpose of this secondary analysis was to determine the comparative responses of markers of inflammation and coagulation potential of healthy adult males consuming diets rich in CSO vs. olive oil (OO). METHODS: Fifteen normal-weight males, ages 21.7 ± 2.58y, completed a randomized crossover trial. Each intervention consisted of a 3-day lead-in diet and a 5-day outpatient, controlled feeding intervention (CSO or OO). There was a 2 to 4-week washout period between interventions. The 5-day intervention diets were 35 % carbohydrate, 15 % protein, and 50 % fat, enriched with either CSO or OO (44 % of total energy from oil). At pre- and post- diet intervention visits, a fasting blood draw was collected for analysis of markers of inflammation (Tumor Necrosis Factor Alpha (TNF-α), Interleukin-6 (IL-6), C-Reactive Protein (CRP)) and coagulation potential (Tissue Factor (TF), Plasminogen Activator Inhibitor-1 (PAI-1)). RESULTS: The CSO-enriched diets reduced TNF-α (CSO: -0.12 ± 0.02 pg/ml, OO: -0.01 ± 0.05 pg/ml; p < 0.01) and TF (CSO: -0.59 ± 0.68 pg/ml, OO: 1.13 ± 0.83 pg/ml; p = 0.02) compared to OO diets. There were no differences in IL-6, CRP, or PAI-1 between diets. CONCLUSION: A 5-day, CSO-enriched diet may be sufficient to reduce inflammation and coagulation potential compared to OO-enriched diets in a healthy male population which could have implications in chronic disease prevention.

Understanding the Role of Polyunsaturated Fatty Acids in the Development and Prevention of Cancer.

Polyunsaturated fatty acids (PUFAs), notably omega-3 (n-3) and omega-6 (n-6), have received much attention owing to their multifaceted effects not only in the management of diverse pathological conditions but also in the maintenance of overall health of an individual. A disproportionately high n-6 to n-3 ratio contributes to the development of various disorders including cancer, which ranks as a leading cause of death worldwide with profound social and economic burden. Epidemiological studies and clinical trials combined with the animal and cell culture models have demonstrated the beneficial effects of n-3 PUFAs in reducing the risk of various cancer types including breast, prostate and colon cancer. The anti-cancer actions of n-3 PUFAs are mainly attributed to their role in the modulation of a wide array of cellular processes including membrane dynamics, apoptosis, inflammation, angiogenesis, oxidative stress, gene expression and signal transduction pathways. On the contrary, n-6 PUFAs have been shown to exert pro-tumor actions; however, the inconsistent findings and controversial data emphasize upon the need to further investigation. Nevertheless, one of the biggest challenges in future is to optimize the n-6 to n-3 ratio despite the genetic predisposition, age, gender and disease severity. Moreover, a better understanding of the potential risks and benefits as well as the cellular and molecular mechanisms of the basic actions of these PUFAs is required to explore their role as adjuvants in cancer therapy. All these aspects will be reviewed in this chapter.

Omega fatty acid ratios and neurodegeneration in a healthy environment.

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Multiple Sclerosis pose substantial public health challenges. While genetics play a primary role, recent research emphasizes the impact of environmental factors, particularly diet and lifestyle. This study investigates the initiating effects of Omega (ω)- 3 and Omega (ω)- 6 fatty acids on neuroinflammation, potentially contributing to these diseases. Using BV-2 microglial cells, we explored the influence of different fatty acid compositions and ratios on cell viability, cytokine production, morphological changes, and lipid peroxidation. Notably, a 2/1 ω-6:ω-3 ratio led to decreased cell viability. Fatty acid compositions influenced cytokine secretion, with reduced TNF-α suggesting anti-inflammatory effects. IL-17 increased, while IL-4 and IL-10 decreased in the 15/1 ω-6:ω-3 ratio, indicating complex cytokine interactions. This study found that polyunsaturated fatty acids interventions induced microglial activation, altering cell morphology even without immunostimulants. These findings demonstrate the intricate nature of fatty acid interactions with microglial cells and their potential implications for neuroinflammation. Further research is needed to clarify mechanisms and their relevance to neurodegenerative diseases, informing possible therapeutic strategies.

Beneficial effects of linoleic acid on cardiometabolic health: an update.

Linoleic acid (LA), as a part of the wider debate about saturated, omega-6 and omega-3 fatty acids (FAs) and health, continues to be at the center of controversy in the world of fatty acid research. A robust evidence base, however, demonstrates that higher intakes and blood levels of LA are associated with improved cardiometabolic health outcomes. LA lowers total and low-density lipoprotein cholesterol when compared with saturated fatty acids and carbohydrates. Using large prospective datasets, higher blood levels of LA were associated with lower risk of coronary heart disease, stroke and incident type-2 diabetes mellitus compared with lower levels, suggesting that, across the range of typical dietary intakes, higher LA is beneficial. Recent trials of LA-rich oils report favorable outcomes in people with common lipid disorders. However, an LA intake that is too high can impair endogenous synthesis of eicosapentaenoic acid (EPA) from alpha-linolenic acid (ALA), but the threshold at which this becomes clinically relevant is not known. In the absence of a significant intake of EPA and docosahexaenoic acid, an ideal dietary ratio of LA and ALA may be theoretically useful as it provides insight into the likely extent of endogenous EPA synthesis from ALA. Updating dietary reference intakes (DRIs) for LA and ALA is needed; however, there are insufficient data to establish RDAs for these fatty acids. The omega-6 (n-6) to omega-3 (n-3) PUFA ratio is not informative and does not shed meaningful insight about the amount of individual fatty acids in each class needed to confer health benefits.

Causal effects of omega-6 and LDL-C on androgenetic alopecia: A Mendelian randomization study.

BACKGROUND: Increasing studies have reported a causal relationship between androgenetic alopecia (AGA) and lipid-related metabolites. However, the relationships between HDL-C, LDL-C, Omega-6, and Omega-3 with AGA remain unclear. Some research findings are even contradictory. Therefore, we designed this study to explore this issue. METHODS: In this study, we selected seven exposure factors, screened SNPs with significant associations, removed linkage disequilibrium and weak instrumental variables, and conducted bidirectional MR analysis. RESULTS: The study found that omega-6 and LDL-C, especially total cholesterol in medium LDL and total cholesterol in small LDL, are risk factors for the occurrence of androgenetic alopecia. CONCLUSION: In summary, we found that various lipid-related metabolites have a causal relationship with the occurrence of androgenetic alopecia, providing new insights into the pathogenesis of androgenetic alopecia and offering references for clinical treatment of androgenetic alopecia.

Association between omega-6 fatty acid intake and asthma in US children and adolescents.

BACKGROUND: Asthma is an inflammatory disease. The potential of omega-6 fatty acids to alleviate asthma symptoms through their anti-inflammatory and immunomodulatory effects has been investigated. However, the association of dietary omega-6 fatty acids in childhood and adolescent asthma remains controversial. OBJECTIVE: The aim of this study was to evaluate the association between dietary intake of omega-6 fatty acids and asthma in children and adolescents in the United States. METHODS: We conducted a cross-sectional analysis of 5045 children and adolescents from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2020. Covariates were adjusted, and multivariate logistic regression, restricted cubic splines, threshold effects, and subgroup analyses were used. RESULTS: Of the 5045 participants, 1000 (19.8%) were identified as having asthma. After adjustment for potential confounders, individuals in the second group (T2, 215.3-377.7 mg/kg/day) had an adjusted odds ratio (OR) of 0.70 (95% CI: 0.57-0.86, P = 0.001) for asthma compared with those in the lowest omega-6 fatty acid intake group (T1, < 215.3 mg/kg/day). Similarly, individuals in the third group (T3, > 377.7 mg/kg/day) had an adjusted OR of 0.59 (95% CI: 0.45-0.78, P < 0.001) for asthma. Furthermore, a non-linear (L-shaped) relationship between omega-6 intake and asthma was observed (P = 0.001), with subgroup analyses confirming the stability of the results. In the threshold analysis, a critical turning point was observed at around 384.2 mg/kg/day (OR = 0.996, 95% CI: 0.995-0.998, P < 0.001). CONCLUSION: The consumption of omega-6 fatty acids in the diet showed an L-shaped association with asthma among children and adolescents in the United States. A critical turning point was noted at approximately 384.2 mg/kg/day.

Long-term effects of abomasal infusion of linoleic and linolenic acids on the enrichment of n-6 and n-3 fatty acids into plasma lipid fractions of lactating cows.

Our objective was to compare abomasal infusions of linoleic (18:2n-6) and α-linolenic (18:3n-3) acids on the enrichment of n-6 and n-3 fatty acids (FA) into the plasma lipid fractions of lactating dairy cows and evaluate their potential carryover effects in plasma lipid fractions postinfusion. Six rumen-cannulated multiparous Holstein cows (252 ± 33 DIM) were fed the same diet and assigned to 1 of 2 treatments in a completely randomized design with repeated measures. Treatments were abomasal infusions (67 g/d total FA) of (1) n-6 FA blend (N6) to provide approximately 43 g/d 18:2n-6 and 8 g/d of 18:3n-3 or (2) n-3 FA blend (N3) providing 43 g/d 18:3n-3 and 8 g/d 18:2n-6. Treatments were dissolved in ethanol, and the daily dose for each treatment was divided into 4 equal infusions, occurring every 6 h. The treatment period lasted from d 1 to 20, and the carryover period lasted from d 21 to 40. Results are presented as FA contents within each of the 4 main plasma lipid fractions: cholesterol esters (CE), phospholipids (PL); triglycerides, and plasma nonesterified fatty acids. Concentrations of individual lipid fractions in plasma were not quantified. Plasma CE and PL had the highest content of PUFA during both the treatment and carryover periods. In plasma PL, N3 increased the contents of total n-3 FA (134%), 18:3n-3 (267%), and eicosapentaenoic acid (96.3%, 20:5n-3), and decreased total n-6 FA (8.14%) and 18:2n-6 (8.16%) from d 4 to 20 compared with N6. In plasma CE, N3 increased the contents of total n-3 FA (191%) from d 4 to 20, 18:3n-3 from d 2 to 20 (178%), and 20:5n-3 from d 6 to 20 (59.9%), while N3 decreased total n-6 FA from d 4 to 20 (11.2%) and 18:2n-6 from d 2 to 20 (10.5%) compared with N6. In addition, compared with N6, N3 decreased arachidonic acid (20:4n-6) at d 2 (45%) and from d 10 to 20 (14.7%) in PL and tended to decrease 20:4n-6 without interacting with time for CE. Phospholipids were the only lipid fraction with detectable levels of docosahexaenoic acid (22:3n-6) in all samples, but we did not observe differences between treatments. In plasma trigylcerides, N3 increased the contents of total n-3 FA (135%) and 18:3n-3 (146%) from d 4 to 20, increased 20:5n-3 from d 12 to 20 (89%), decreased or tended to decrease total n-6 FA content from d 6 and 8 (26.9%), and tended to decrease 18:2n-6 at d 8 compared with N6. A similar pattern was observed for plasma nonesterified FA. We observed positive carryover effects for both N3 and N6 at different degrees in all lipid fractions, with N3 promoting more consistent outcomes and increasing total n-3 FA throughout the carryover period (from d 22 to 40) in both PL (52.8%) and CE (68.6%) compared with N6. It is important to emphasize that the higher magnitude responses observed for n-3 FA are also influenced by the content of n-3 FA being much lower than those of n-6 FA in all lipid fractions. Although these data provide important and robust information, future research quantifying changes in concentrations of individual lipid fractions in plasma and the entry and exit rates of specific FA will further enhance our understanding. In conclusion, abomasally infusing N3 and N6 increased the contents of n-3 and n-6 FA, respectively, in all plasma lipid fractions. These responses were more evident in PL and CE. We also observed positive carryover effects in all lipid fractions, where N3 had more consistent outcomes than N6. Our results indicate that dairy cows have a robust mechanism to conserve essential FA, with a pronounced preference for n-3 FA.

Ameliorative effects of omega-3 and omega-6 on spermatogenesis, testicular antioxidant status and in vivo fertility index in heat-stressed rats.

The current study aimed to investigate the use of omega-6 (ω6) or omega-3 (ω3) in reducing heat-induced damage to the testicles. This is due to the known detrimental effects of heat and the potential protective properties of ω6 and ω3. In the study, 48 male rats were divided into eight groups, each containing 6 rats. Group I (control) received normal saline. Group 2 was exposed to high temperatures (43 °C for 20 min/day) and also received normal saline for 60 days. Groups 3-7 underwent identical HS conditions and received varying doses of ω6 or ω3 (0.5 mg/kg DHPG, 1 mg/kg DHPG, 5 mg/kg HT, 0.5 mg/kg DHPG + 5 mg/kg HT, and 1 mg/kg DHPG + 5 mg/kg HT), respectively. After 60 days, various tests were conducted on the testicular tissue, sperm quality, oxidative status, gene activity, and in vivo fertility indexes to evaluate the effects of the treatments. Treatment with ω6 and ω3 could reduce abnormal morphology and DNA damage while increasing total and progressive motility, characteristics motility, viability, and plasma membrane functional impairment compared with HS-exposed groups. Antioxidant status levels in testicular tissue were improved after administration of ω6 and ω3. Furthermore, after receiving ω6 and ω3, there were significantly lower expression levels of P53 and Caspase-3 and significantly higher expression levels of Bcl-2 compared to the HS-exposed group. Furthermore, the results showed that administration of ω6 and ω3 to rats exposed to HS could increase their in vivo fertility indexes compared to the group not exposed to HS. According to our data, all doses of ω6 and ω3 (particularly doses of ω6-1.25 and ω3-300) can improve the testicular damage, testicular antioxidant defense mechanism, regulate germ cell apoptosis, and increase in vivo fertility indexes.

Dietary ratio of linoleic to alpha-linolenic acid affects the reproductive performance of Japanese quail.

1. This study was conducted to assess the effects of different dietary omega 6:3 ratios fed to male and female Japanese quail breeders on incubation performance, chick quality and progeny performance.2. A completely randomised design was used, with five diets containing different ratios of vegetable oils rich in linoleic acid (LA from soybean oil) or α-linolenic acid (ALA from linseed oil) with LA/ALA ratios of 13.75:1, 10.69:1, 7.63:1, 4.57:1 and 1.48:1 with 12 cage replicates containing six birds each.3. There was a quadratic effect of the LA/ALA ratio on total hatchability (p < 0.011), fertile hatchability (p = 0.046) and total mortality (p = 0.046). There was no effect on fertility (p > 0.05). The LA/ALA ratios of 1.48 and 13.75 fed to both hens and cockerels or hens resulted in greater fertility, as measured by the number of days after copulation during which fertile eggs were laid and the number of points of hydrolysis on the perivitelline membrane. A decreasing linear effect (p < 0.0001) was observed on chick length and an increasing linear effect on body weight at 1 day of age. There were no effects on progeny performance.4. The LA/ALA ratio affected yolk mineral matter (p = 0.009), crude protein (p = 0.091), chick mineral matter (p < 0.038) and ether extract (p < 0.0001) contents. Maternal diet affected the fatty acid profile of egg yolk and chick liver, indicating that dietary contents were transferred to eggs and chicks.5. Fertile egg production increased with lower LA/ALA ratios. Therefore, linseed oil can be used together with soybean oil to formulate diets for female Japanese quail obtain LA/ALA ratios between 4:1 and 10:1.

Analysis of omega-3 and omega-6 polyunsaturated fatty acid metabolism by compound-specific isotope analysis in humans.

Natural variations in the 13C:12C ratio (carbon-13 isotopic abundance [δ13C]) of the food supply have been used to determine the dietary origin and metabolism of fatty acids, especially in the n-3 PUFA biosynthesis pathway. However, n-6 PUFA metabolism following linoleic acid (LNA) intake remains under investigation. Here, we sought to use natural variations in the δ13C signature of dietary oils and fatty fish to analyze n-3 and n-6 PUFA metabolism following dietary changes in LNA and eicosapentaenoic acid (EPA) + DHA in adult humans. Participants with migraine (aged 38.6 ± 2.3 years, 93% female, body mass index of 27.0 ± 1.1 kg/m2) were randomly assigned to one of three dietary groups for 16 weeks: 1) low omega-3, high omega-6 (H6), 2) high omega-3, high omega-6 (H3H6), or 3) high omega-3, low omega-6 (H3). Blood was collected at baseline, 4, 10, and 16 weeks. Plasma PUFA concentrations and δ13C were determined. The H6 intervention exhibited increases in plasma LNA δ13C signature over time; meanwhile, plasma LNA concentrations were unchanged. No changes in plasma arachidonic acid δ13C or concentration were observed. Participants on the H3H6 and H3 interventions demonstrated increases in plasma EPA and DHA concentration over time. Plasma δ13C-EPA increased in total lipids of the H3 group and phospholipids of the H3H6 group compared with baseline. Compound-specific isotope analysis supports a tracer-free technique that can track metabolism of dietary fatty acids in humans, provided that the isotopic signature of the dietary source is sufficiently different from plasma δ13C.

The role of polyunsaturated fatty acids in neuronal signaling in depression and cognitive processes.

This study aimed to evaluate research findings on the role of polyunsaturated fatty acids (PUFAs) in neuronal signaling. Polyunsaturated fatty acids (PUFAs) are the building blocks of the brain and are responsible for the proper functioning of neurons, synapses, and neuronal communication. The deficiency of a significant component, omega-3 (ω-3) FA, in favor of omega-6 (ω-6) FA can exacerbate the course of mental illness and be one of the triggers of the cascade of neurodegenerative changes. PUFAs play an essential role in transmitting neuronal signals, affecting brain homeostasis. Physicochemical parameters of lipid layers significantly affect their functioning; interactions between lipids and proteins in brain cells are critical for mechanical stability and maintaining adequate elasticity for vesicle budding and membrane fusion. This paper discusses the role of PUFA deficiency or inappropriate ratios in brain tissue. The deficiency is a crucial element in depressive disorders and cognitive impairment, while in Alzheimer's disease, there is some controversy.

Systemic Lupus Erythematosus and the Ratio of Omega-3 to Omega-6 Fatty Acids Consumption among Women in the Adventist Health Study-2.

OBJECTIVE: To assess the associations of omega-3 and omega-6 fatty acids consumption, and the ratio between the two, with self-reported doctor told Systemic Lupus Erythematosus (SLE) diagnosis. Further, to assess whether initiation of omega-3 supplements intake was related to time/year of SLE diagnosis. METHODS: Data from 42,398 women in the Adventist Health Study-2 cohort were used for this cross-sectional study. Unconditional logistic regression modeling was used for all analyses with the following candidate covariates: age, race, education, smoking, and body mass index (BMI). RESULTS: Compared to non-cases, participants with a diagnosis of SLE reported higher intakes of total omega-3 fatty acids and about the same intakes of omega-6 fatty acids. Overall, they had higher ratios of omega-3 to omega-6 fatty acids. When assessing odds ratios of SLE diagnosis by quartiles of omega-3 to omega-6 and DHA+EPA to omega-6, there was a positive significant trend (p trend = 0.005). Additionally, among those reporting intake of fish oil, 87% had initiated fish oil consumption around the time of SLE diagnosis. SLE was more likely to occur among Black women compared to White women, among ever smokers compared to never smokers, among overweight women compared to women with normal/underweight, and among women 50-59 years compared to those 30-49 year old. When a smaller 6 year follow-up study identified 64 incident SLE cases and assessed their omega-3 intake at baseline (6 years earlier and before the SLE diagnosis) their intake of omega-3 and fish oil was no different than among non-cases. CONCLUSION: We observed a significant positive association between the ratio of omega-3 to omega-6 fatty acids consumption and prevalence of SLE. Among those with prevalent SLE, their year of starting supplementation of omega-3 and fish oil was closely linked to year of SLE diagnosis. Further, baseline intake of omega-3 fatty acids was not increased among 64 incident SLE cases identified during 6 years of follow-up. Our surprising finding can best be explained by reverse causation. This could be an example of how public health information is assimilated and acted upon by a health conscious public.

Blood levels of omega-6 fatty acids and coronary heart disease: a systematic review and metaanalysis of observational epidemiology.

Individual omega-6 polyunsaturated fatty acids (PUFAs), principally linoleic acid (LA) and arachidonic acid (AA), may have differential impacts on cardiovascular risk. We aimed to summarize the up-to-date epidemiology evidence on the relationship between blood levels of omega-6 PUFAs and the risk of coronary heart disease (CHD). Population-based studies determining PUFA levels in blood were identified until May 2021 in PubMed, Embase, Web of Science, and Cochrane Library. Random-effects meta-analyses of cohorts comparing the highest versus lowest category were conducted to combine study-specific risk ratios (RRs) with 95% confidence intervals (CIs). Blood levels of omega-6 PUFAs were compared between the CHD case and non-case, presented as a weight mean difference (WMD). Twenty-one cohorts and eleven case-control studies were included. The WMD was -0.71 (95% CI: -1.20, -0.21) for LA and 0.08 (95% CI: -0.28, 0.43) for AA. LA levels were inversely associated with total CHD risk (RR: 0.85, 95% CI: 0.71, 1.00), but not AA. Each one-SD increase in LA levels resulted in 10% reductions in the risk of fatal CHD (RR: 0.90, 95% CI: 0.86, 0.95), but not in non-fatal CHD. Such findings highlight that the current recommendation for optimal intakes of omega-6 PUFAs (most LA) may offer a coronary benefit in primary prevention.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2056867 .

Unraveling the role of natural functional oils in modulating osteoarthritis related complications.

Osteoarthritis (OA) is a common joint disease and has been studied extensively in recent years as no promising therapy available so far for its treatment and remains a great challenge for health care specialists. Although the identification of some major mechanisms that contribute to this disease suggests a plethora of bioactive agents in tackling the associated complications yet OA's pathophysiology is still poorly understood owing to complex mechanistic changes observed. Experimental research is now exploring a wide range of therapeutically effective agents in an effort to find a way to repair OA-related joint degeneration and halt it from getting worse. Data was acquired and reviewed from most relevant and recent studies. This review summarizes the studies that are currently available and focuses on how various unconventional functional oils affect osteoarthritis and the affected joint tissues. An analysis of the recent scientific literature allowed us to highlight the potential anti-arthritic properties of edible oils and their main constituents, which seems to suggest an interesting new potential therapeutic application. Due to eccentric nature of OA, it is necessary to concentrate initially on the management of symptoms. The evidence supporting functional oils chondroprotective potential is still accumulating, underpinning a global need for more sustainable natural sources of treatment. More clinical research that focuses on the consequences of long-term treatment, possible negative effects, and epigenetic implications is necessary to get optimistic results. However, different animal or clinical studies suggest that linolenic and linoleic fatty acids decreased chondrocyte oxidative stress, cartilage breakdown, and expression of inflammatory markers. Distinct fatty acids along with minor components of oils also reduced the generation of prostaglandins and decreased oxidative stress. Furthermore, the potential roles of the main components of edible oils and possible negative results (if any) are also reported. While no severe side effects have been reported for any edible oils. Overall, these studies identify and support the use of functional oils as an adjuvant therapy for the management of OA and as a means of symptomatic alleviation for OA patients. However, to prove the effectiveness or to draw precise conclusions, high-quality clinical trials are required.

Dietary intake and biomarkers of linoleic acid and risk of prostate cancer in men: A systematic review and dose-response meta-analysis of prospective cohort studies.

Findings on the association of dietary intake and tissue biomarkers of linoleic acid (LA) with the risk of prostate cancer are conflicting. Also, no meta-analysis summarized available findings in this regard. Therefore, the current systematic review and dose-response meta-analysis were done to summarize the findings of prospective cohort studies that assessed dietary intake and tissue biomarkers of LA in relation to prostate cancer risk in adults. We conducted a systematic search using online databases, including PubMed, Scopus, and ISI Web of Science, to identify eligible articles published up to January 2023. We included prospective cohort studies that examined the associations of dietary intake and tissue biomarkers of LA with the risk of prostate cancer (total, advanced, and fatal prostate cancer). Summary relative risks (RR) and 95% confidence intervals (CI) were calculated for the highest versus lowest intakes/tissue levels of LA using a fixed-effects model. Also, linear and non-linear dose-response analyses were conducted. In total, 15 prospective cohort studies were included. These studies recruited a total sample size of 511,622 participants with an age range of ≥18 years. During the follow-up periods ranging from 5 to 21 years, 39,993 cases of prostate cancer, 5,929 cases of advanced prostate cancer, and 1,661 cases of fatal prostate cancer were detected. In the meta-analysis, we found that higher tissue levels of LA were associated with a reduced risk of prostate cancer (RR: 0.86, 95% CI: 0.77-0.96) so that in the dose-response analysis, each 5% increase in levels of LA was associated with a 14% lower risk of prostate cancer. Such a significant association was not seen for advanced prostate cancer (RR: 0.86, 95% CI: 0.65-1.13). Also, we found no significant association between dietary intake of LA and risk of total (RR:1.00, 95% CI: 0.97-1.04), advanced (RR: 0.98, 95% CI: 0.90-1.07), and fatal prostate cancer (RR: 0.97, 95% CI: 0.83-1.13). Our findings support the protective association between tissue levels of LA and the risk of prostate cancer in men.